There may be an activation of the immuno-inflammatory response system in fibro. Here are some of the 30-plus studies. 2014-2015 studies edited into the top. I may not edit in as many links in the future cuz a moderator feels I have made this too long.
If you think you may want this info for future reference, I suggest you save a copy. It may be deleted by the moderator.
Published March 2017
Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma. /www.ncbi.nlm.nih.gov/m/pubmed/28424559/
11/8/2015 Presentation @ meeting of American College Rheumatology & AHRP
Higher Levels of Pro-Inflammatory and Lower Levels of Anti-Inflammatory Cytokines Are Present in Fibromyalgia Patients/www.healingwell.com/community/default.aspx?f=24&m=3548138
"There were no statistically significant changes in biomarker levels, although total group C-reactive protein [CRP] was elevated at baseline (4.7 mg/L), indicating an inflammatory process. "
Title: Effects of guided imagery on biobehavioral factors in women with fibromyalgia. [number: 72 women]
Journal of Behavioral Medicine 2014. Menzies et al./www.infona.pl/resource/bwmeta1.element.elsevier-e4fed0b8-cde6-3d04-9403-31db1f348765
Mostly I link to abstracts/studies, but here is a more easily read blog from Cort Johnson which was posted after publication of the next linked study from Spain, about
the mitochondria. It's a safe bet to rely on Cort's blogs at HealthRising and SimmaronResearch. I followed him on Facebook.www.cortjohnson.org/blog/2015/03/04/is-fibromyalgia-a-mitochondrial-disorder/
Oxidative stress, mitochondrial dysfunction and, inflammation common events in skin of patients with Fibromyalgia. (This team is with Cordero, whose name is on a depression/amitriptyline study about
amitriptyline being mitotoxic, as well as other (fibro) studies. Also see the study about
amitriptyline damaging fibroblasts, before considering taking it. Both studies are posted at myPatientMatch.)/www.infona.pl/resource/bwmeta1.element.elsevier-e4fed0b8-cde6-3d04-9403-31db1f348765
Post edit. Since the time of the study below, a study has found higher factalkine in cerebral spinal fluid of fibro patients.
Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma/www.ncbi.nlm.nih.gov/pmc/articles/PMC5344444/
Garcia et al. 2014
This study found lower fractalkine in fibro. It is an inflammatory chemokine. They are saying perhaps fractalkine levels can distinguish fibro patients from others, which would be helpful in diagnosis. Their use of the word "most" is perhaps important.
"Plasma from female patients with fibromyalgia had lower levels of fractalkine cytokines than healthy control patients, according to results of a recently published study."
"Plasma analysis of levels of fractalkine, an inflammatory chemokine with chemotactic activity for monocytes that mediates pain..."
“Since most inflammatory pathologies show elevated plasma levels of soluble fractalkine, the results may contribute towards a differential diagnosis for fibromyalgia.”sacfs.asn.au/news/2014/12/12_18_specific_cytokine_lower_in_fibromyalgia_patients.htm
Publ. in Anais da Academia Brasileira de Ciências (Annals of the Brazilian Academy of Sciences) official journal of Academia Brasileira de Ciências (Brazilian Academy of Sciences). It has been published with no major interruptions since 1929, but is older than that.
December 16, 2014
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Kosek, Kadetoff, Lampa et al.
On the fibromyalgia side of this next study (vs. their cohort with arthritis), the team duplicates their earlier fibro findings. It's useful reading in 2 respects. First that their team demonstrates once again that they can find intrathecal IL-8/interleukin-8, an inflammatory cytokine. (Intrathecal: in the theca/sac of the spinal cord.) In the introduction they explain that they want to try to figure out what is driving the change to heart rate variability in fibro patients. They discuss their curiosity about
autonomic systems, sympathetic vs. parasympathetic nervous systems. Edit Oct 20, 2015: They also explain the importance of glia cell activation in the intro. Just reading about
glia & neuroinflammation in the intro could be helpful to fibro newbies.
In an earlier study (Kadetoff et al) they offered that their finding of intrathecal IL-8 suggests possible glia cell activation as a cause for the start of chronic pain in fibromyalgia. Glia cells are brain/CNS immune cells which may be causing neuroinflammation by releasing inflammatory cytokines. (For more studies related to glia cell activation and its possible influence on chronic pain states, via the release of inflammatory cytokines, you may also wish to see the works of teams with Linda Watkins, Phd., but this Kosek et al. fibro study is of course footnoted. I think the intro is worth reading to help grasp glia cell activation.)
Study Title: Evidence of different mediators of central inflammation in dysfunctional and inflammatory pain — Interleukin-8 in fibromyalgia and interleukin-1 β in rheumatoid arthritis. Kosek, Lampa, Kadetoff, etc et al. Journal of Immunology MAR 2015. A refereed publication.www.sciencedirect.com/science/article/pii/S0165572815000351
LDN ° LDN ° LDN ° LDN ° LDN ° LDN ° LDN ° LDN ° LDN ° LDN ° LDN °LDN °LDN ° LDN
Title: The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. By Younger, Parkitney, & MacLain. Published Oct. 2014 in Clin. Rheum. Covers both a 2009 pilot study and a larger 2012 fibromyalgia study. LDN may be influencing/blocking Toll-like receptor 4 / TLR4 on glia cells. (Tho other receptors are possibilities.) Not sure my memory is right, I have no medical background, but I'm thinking they said Toll-like receptors are also found on microglia. It's interesting to me that they found LDN lowered peripheral inflammation, too.
[ESR= erythrocyte sedimentation rate. An inflammatory marker. ESR or SED] "Aggregating across studies (Fig. 2), we see that fibromyalgia patients with greater ESR
levels at baseline tend to have greater pain reduction when taking LDN ..... In contrast, there is no association between baseline ESR and pain reduction during placebo administration..." They screened for ESR/SEDimentation rate prior to treatment and later analysis revealed that those with higher SED rates at the start had more relief from pain than others that used LDN.
"We have shown in two separate, small clinical trials that LDN may be an effective treatment for FM."
Before ever using LDN I recommend reading about
the experiences of other patients who have or are trying it & are periodically updating their reviews. A great source of info and help are the treatment reviews and other discusions of LDN at my patient match. Omit the spaces, (I am trying out writing it like that here)
Many patients need to start at extremely low doses, and how they do that is helpful. Other tips that I have read there could be the difference between success and failure.
Hashimotos patients may have thyroid hormone output improve, and must be alert
to not become hyperthyroid for too long. Be ready: dosing adjustments for thyroid hormone may be needed.
--And all should realize LDN must still be considered experimental. I think there are over 80 of LDN reviews on the treatment review side of that site as of Oct. 2015. I wonder if some of the people who tried it early on would have been successful had they had some of the advice/experience of others.www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/
Edit February 29, 2016. This is an interview with Jarred Younger. There is much discussion of glial cells and neuroinflammation. I believe it is a "must read" for the scientifically inclined, at this point in time.www.cortjohnson.org/blog/2015/07/15/the-neuroinflammation-man-jarred-younger-on-inflammation-fibromyalgia-and-chronic-fatigue-syndrome/
Edit: April 24, 2017. Younger's team member, Parkitney, was the lead on a team, and was published for a follow-up LDN study and found that after 8 weeks of low dose naltrexone, inflammatory cytokines were lowered. This Healingwell thread has interesting info from their UAB Neuroinflammation Lab. www.healingwell.com/community/default.aspx?f=24&m=3834485
NLRP3 Inflammasome Is Activated in Fibromyalgia: The Effect of Coenzyme Q10.
Results: Mitochondrial dysfunction was accompanied by increased protein expression of interleukin (IL)-1β, NLRP3 (NOD-like receptor family, pyrin domain containing 3) and caspase-1 activation, and an increase of serum levels of proinflammatory cytokines (IL-1β and IL-18).
Innovation: These results show an important role for the NLRP3 inflammasome in the pathogenesis of FM, and the capacity of CoQ10 in the control of inflammasome.
Cordero et al. (They also have other interesting fibro studies. Those can be found by searching with the keywords: study abstract firomyalgia Cordero, ROS, LPO's, mitochondria )
This one was published in: Anti-oxidants and Redox Signaling. Mar 2014.www.ncbi.nlm.nih.gov/pmc/articles/PMC3934515/
Someone who has chemistry degree gave me a link about
the differences between ubiquinol and ubiquinone, and I have not read the info yet. (In response to my remark about
all of the newer research about
ubiquinol being better than plain ol' CoQ-10.). He also said some patients prefer ubiquinone over ubiquinol, and for others the reverse is true.
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Post edited June 2014. I'm adding in some more study titles and quotes right here that I've found since this thread was first posted:
Xiao et al.
(Univ. TX Med San Antonio. Dr. Jon Russell was also on this team). They used high-sensitivity C-reactive protein tests (CRP
indicates inflammation) in a fibro study and found patients with higher hs-CRP in the fibro group. There were correlations with higher ESR (erythrocyte sedimentation rate
: elevations point toward inflammation), IL-8 (inflammatory cytokine), IL-6 (can be an inflammatory cytokine).
Then in another study they looked for a genetic polymorphism for that and found that a genetic SNP (pronounced "snip", Single Nucleotide Polymorphism) for the gene: brain derived neurotropic factor/BDNF was associated with higher CRP ....I think only when it was also accompanied by higher BMI/Body Mass Index. (remember that some genes must be turned on before they are expressed but fyi, I'm not very knowledgeable about
Xiao et al has also discovered statistics for elevated ESR (SED or erythrocyte sedimentation rate) in a fibro cohort. ESR or SED
indicates inflammation in the body.www.ncbi.nlm.nih.gov/m/pubmed/23124693/?i=2&from=/21773883/related
Earlier this study found that inflammatory markers in fibro are found independent of having a higher Body Mass Index.www.ncbi.nlm.nih.gov/pmc/articles/PMC2891797/
Fibromyalgia: Anti-Inflammatory and Stress Responses after Acute Moderate Exercise. Exercise reduced the numbers of IL-8, an inflammatory cytokine found in FMS. (also a cortisol finding).
(PlosOne is a peer reviewed publication.)www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0074524
Pernambucom et al. Clin Ex Rheum. 2013 Nov-Dec;31.
The analyses showed that fibromyalgia patients present increased levels of IL-17A. They also revealed that plasma concentrations of IL17A positively correlate with levels of IL-2, IL-4 and IL-10, TNF and IFNγ.
As far as we are aware, this is the first study to demonstrate increased levels of IL-17A in fibromyalgia patients. The positive correlation between the levels of IL-17A and of other cytokines strengthens the hypothesis of the involvement of inflammatory mechanisms in the development of this syndrome.www.ncbi.nlm.nih.gov/pubmed/24021410
Title: Discovery of potential new gene variants and inflammatory cytokine associations with fibromyalgia syndrome by whole exome sequencing. Feng et al. PLOS ONE June 10, 2013 (PLOSONE is a peer reviewed publication)
"The subset with the C11orf40 mutation had elevated plasma levels of the inflammatory cytokines, MCP-1 and IP-10, compared with unaffected controls or FMS patients with the wild-type allele. Similarly, patients with the ZNF77 mutation have elevated levels of the inflammatory cytokine, IL-12, compared with controls or patients with the wild type allele. Our results strongly implicate an inflammatory basis for FMS, as well as specific cytokine dysregulation, in at least 35% of our FMS cohort."www.ncbi.nlm.nih.gov/pubmed/23762283
Plasma Cytokine Fluctuations over Time in Healthy Controls and Patients with Fibromyalgia. [discusses release of pro-inflammatory and anti-inflammatory cytokines in a 24 hr period. Anti-inflammatory cytokines down-regulate inflammation from the proinflammatory cytokines.]
Fumiharu Togo et al.Experimental Biology and Medicine/ The Royal Society Of Medicine Journals. (A peer reviewed journal.)Feb. 2009 ebm.sagepub.com/content/234/2/232
There is info about
chemokines in the intro of this study if you want to understand what they can do.
Title: Altered profile of chemokines in Fibromyalgia patients.
"Based on the assumption that the origin of all pain is inflammation and the inflammatory response, special attention has been paid to the inflammatory hypothesis of FM with the implication of inflammatory cytokine involvement in the syndrome and in the modulation of pain. Although there are conflicting results related to cytokine levels,[15,16] FM might be caused by a mild inflammatory condition, since most FM patients show elevated concentrations of serum IL-8,[15,17⇓–19] of IL-6 in the supernatants of peripheral blood mononuclear cells (PBMC), and of IL-1β, TNF (tumor necrosis factor)-α, IL-6 and IL-10 in the supernatants of isolated monocytes. However, chemotactic cytokines, or chemokines, have been little studied in people with FM, with just a single study showing that MCP-1 (monocyte chemotactic protein-1) and eotaxin concentrations are elevated in the plasma of women with FM.
"In previous studies by our research group, we found that FM patients have a high systemic concentration of IL-8 (CXCL8), [18,19] but normal values of the pro-inflammatory cytokines TNF-α, IL-1β, IL-2, IL-6 and IL-18 and of the anti-inflammatory cytokines IL-10 and IL-4.
[Note from Rockon: as I recall, other studies have different findings about
TNF-α and IL6.]
"As well as being a pro-inflammatory cytokine, IL-8 is also considered to be an inflammatory chemokine since it is a potent chemoattractant for neutrophils  (cells essential for the development of the inflammatory response), besides being a potent promoter of sympathetic pain.19,24"
"Results: FM patients had elevated serum levels of the following inflammatory chemokines: TARC (P < 0.001), MIG (P < 0.001), MDC (P < 0.01), I-TAC (P < 0.01) and eotaxin (P < 0.05). No differences were found in the circulating concentrations of PARC and HCC-4 (homoeostatic chemokines)."
Garcia et al. Annals of Clinical Biochemistry. October 8, 2013 ("The Annals of Clinical Biochemistry: International Journal of Laboratory Medicine publishes fully refereed papers of international authorship that contribute to existing knowledge in all fields of laboratory medicine...." acb.sagepub.com/content/early/2013/10/04/0004563213506413.full
Title: A subset of fibromyalgia patients have findings suggestive of chronic inflammatory demyelinating neuropathy and appear to respond to IVIG. Caro et al. Oxford Journals 2007
Results. "... EDX demonstrated a distal demyelinating polyneuropathy, suggestive of chronic inflammatory demyelinating polyneuropathy (CIDP)."rheumatology.oxfordjournals.org/content/47/2/208
Non-fibro but relevant study:
"Although basic research on neuroimmune interactions suggests that inflammatory processes may play a role in the development of fatigue, population-based evidence on this association is limited. This study examined whether plasma C-reactive protein (CRP)
[an "acute phase" protein]and interleukin-6 (IL-6), biomarkers of systemic inflammation, predict fatigue onset....
Plasma CRP and IL-6 were prospectively associated with new-onset fatigue, supporting the hypothesis that low-grade inflammation has a role in the development of fatigue."
Title: Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study. Cho et al. August 2013www.ncbi.nlm.nih.gov/pubmed/23151405
A subset of fibro patients show higher C-reactive Protein (CRP) in bloodwork.
IL-6 is found in fibro studies.
One source said 58% of women with fibro have CFS and over 70% of the men do also. Another source I've seen put the number at 70% without dividing by gender.
A study of CFS/chronic fatigue found neuroinflammation:www.sciencedaily.com/releases/2014/04/140404085538.htm
A little off topic:
Jerrod Younger et al. (LDN studies) did a thorough study measuring inflammatory cytokines (51of them I think) every single day in CFS patients. Analysis revealed that by looking at leptin levels it was possible to predict which days CFS patients said were their worst days. btw, Leptin [a hormone, I believe] studies in fibro are a mixed bag and their methods do not compare to Younger's. Testing for each fibro patient was done on one day only. The NIH has already funded another CFS study by Younger (to be done at Univ. Alabama in Birmingham).
Metal-induced inflammation triggers fibromyalgia in metal-allergic patients.[has info about
metal in the mouth, mercury amalgam fillings] Stejskal et al. www.researchgate.net/publication/260368263_Metal-induced_inflammation_triggers_fibromyalgia_in_metal-allergic_patients
Sturgill et al.
This study is a bit more complicated, finding that there is possibly immune system dysfunction, one system being more dominant than another, based on which cytokines (from which TH<--T helper-- systems) have been observed by their team. (Those tested cytokines had to meet a criteria of being 2X the level reported as the norm in healthy subjects in the literature, to be taken in to consideration.)
Journal of Immunology Research [This journal is refereed and has an international editorial board) 2014. Sturgill et
....The purpose of this analysis was to examine cytokine alterations in patients with FMS that were not determined a priori. Comparing the observed cytokines in the plasma of these patients we noticed a stark decrease in the amount of cytokines produced (IL-4, IL-5, and IL-13) as those values reported by other groups in the literature. We extended our analyses to include a secondary, independent data set and once again this unique cytokine signature was observed.
To examine a potential underlying cause for the suppression, we then correlated cytokine levels to pain, stress, fatigue, and depression which are all symptoms shared in the FMS spectrum. When pain and levels were compared we observed a trend that approached statistical significance. Interleukin 4, the classic cytokine has been shown to have both anti-inflammatory and analgesic properties in murine [rodent] models of mechanical  as well as having lower gene expression and serum levels in patients with widespread pain syndromes . IL-13 exhibits analgesic properties in a murine [rodent] model of L. major infection , whereas little is reported in regard to IL-5’s ability to combat pain.Thus our preliminary findings suggest that further research into the TH1 TH2 [the 2 principles of the 3 discovered immune systems] imbalance in FMS and its implication in pain are certainly warranted....
_______original thread post begins here________
Aside from studies I am posting which find inflammatory cytokines and chemokines in fibromyalgia patients, studies have also looking at levels of anti-inflammatory cytokines in FMS patients, and finding fewer of them. This is significant because their role is to down-regulate inflammation from the proinflammatory cytokines.
I have started with this from July 2001, but then I am skipping around in time. The earliest I have found is the 1999 study from Michael Maes.
Wallace et al. Journal of Rheumatology
"Dr. Daniel Wallace headed up an investigation in Los Angeles discovering that patients sick for over two years were more likely to have high cytokines levels. Although the researchers found altered cytokine production in early-stage fibromyalgia, the cytokines were seen to increase with the duration of the sickness. The authors of this work conclude that their results underscore "the argument for earlier, aggressive intervention to prevent a chronic pattern from developing."
"It has not yet been determined, however, whether elevated cytokines are the direct cause of fibromyalgia or merely secondary to another factor. Factors that could contribute to cytokines increase and be a more direct cause of the ailment are other immune problems, abnormal hormone activity, or sleep disturbances. For example, elevated cytokine levels can be induced through sleep deprivation, so perhaps disordered sleep could be the real root of fibromyalgia.
"Other researchers feel the same about
this possible cause of CFS, despite the mixed result seen in studies performed. Dr. Stephen Straus writes, "An immune disturbance of some type, though, is in line with one favored theory that many of the symptoms of chronic fatigue syndrome derive from excessive cytokine release."
"Management of Cytokine Inflammation"
Dr. Roberto Patarca has extensively studied the topic and he says medications are not available "mainly because nobody knows which cytokine system in particular to target and because of the [complexity] of the cytokine network components." But research on this topic continues
From: Cytokine Inflammation and Management in Fibromyalgia and Chronic Fatigue Syndrome By John W. Addington. www.prohealth.com/library/showarticle.cfm?libid=8610
TITLE: Is there a role for cytokine based therapies in fibromyalgia? By Dr. Danial Wallace. 2006.www.eurekaselect.com/55246/article
Evaluation of vascular injury with proinflammatory cytokines, thrombomodulin and fibronectin in patients with primary fibromyalgia.
Pay S1, Calgüneri M, Calişkaner Z, Dinç A, Apraş S, Ertenli I, Kiraz S, Cobankara V.
Nagoya Journal of Medical Science 2000, 63:115-122. PubMed Abstract
I cannot find this again, so I cannot provide a link. I don't know why that might be.
Evidence of Central Inflammation
in fibromyalgia — Increased Cerebralspinal Fluid
Diana Kadetoff, Jon Lampa, Marie Westman, Magnus Andersson, Eva Kosek (follow up study Mar 2015 found intrathecal IL-8 again, looked at more cytokines. They looked also at RA patients in 2015)
Activation of glia cells resulting in intrathecal [in the theca/sac of the spinal cord] elevation of cytokines and chemokines has been hypothesized in chronic pain syndromes such as fibromyalgia. To our knowledge, this is the first study assessing intrathecal concentrations of pro-inflammatory substances in fibromyalgia. We report elevated cerebrospinal fluid and serum concentrations of interleukin-8, but not interleukin-1beta, in FM patients. This profile is in accordance with FM symptoms being mediated by sympathetic activity rather than dependent on prostaglandin associated mechanisms and supports the hypothesis of glia cell activation in response to pain mechanisms.
You can find evidence of IL-8 and TNF-a (alpha), another proinflammatory cytokine, in various fibromyalgia studies. For example this one:
Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Bazzichi et al. Department of Internal Medicine, Division of Rheumatology, University of Pisa, Pisa, Italy
Eighty FM patients underwent clinical and psychiatric evaluations, and plasma levels of cytokines (IL-1, IL-6, IL-8, IL-10, TNF-alpha), aspecific markers of inflammation, rheumatoid factor (RF), anti-extractable nuclear antigen (ENA) antibodies, and anti-nuclear factor (FAN) were measured.
Higher levels of IL-10, IL-8 and TNF-alpha were found in FM patients than in controls. Significant correlations between the biochemical parameters and clinical data were found.
The higher levels of cytokines found in FM patients suggest the presence of an inflammatory response system (IRS) and highlight a parallel between the clinical symptoms and biochemical data. They support the hypothesis that cytokines may play a role in the clinical features of fibromyalgia. In addition, the similar cytokine patterns found in FM patients with different psychiatric profiles suggests that IRS impairment may play a specific role in the disease.
Üçeyler N, Valenza R, Stock M, Schedel R, Sprotte G, Sommer C
Arthritis and Rheumatology. 2006.
Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain.www.ncbi.nlm.nih.gov/pubmed/16871547
Maes M, et al. 1999 May. Published in Psychneuroendocrinology. (This is one of my favorite researchers. You won't find him assuming an illness is psychosomatic, and he will set out to prove that something isn't. For example one of his studies demonstrates that it's dangerous to an ME/CFS patient to treat them as if the illness can be turned around with CBT and GET. Another finds inflammation in depression, another connects gut health to depression.)
The immune-inflammatory pathophysiology of fibromyalgia: increased serum soluble gp130, the common signal transducer protein of various neurotrophic cytokines.www.ncbi.nlm.nih.gov/pubmed/10341365
(Repeat) Hernandez et al. Proinflammatory cytokine levels in fibromyalgia patients are independent of body mass index.www.biomedcentral.com/1756-0500/3/156
Cytokine expression in whole blood of patients with FMS was investigated in one study including 26 FMS patients and 40 healthy controls . The study had a modified CEMB level of 3d, a NOS of 4 and was of high methodological quality and found reduced levels of the anti-inflammatory cytokines IL-4 and IL-10 gene expression in FMS patients compared to controls. These results were not reproduced.....
A significant difference between controls and FMS was found only in two subgroups. When analyzing data of three studies on the pro-inflammatory cytokine IL-6 plasma levels investigated with ELISA or immunoassay or bioplex assay, patients with FMS had higher plasma levels of IL-6 compared to controls (SMD, -0.34; [-0.64, -0.03] 95% CI; p = 0.03; Table 4). There was also a trend for elevated serum IL-6 levels in FMS patients compared to controls (SMD, 1.01; [-0.03, 2.05] 95% [CI]; p = 0.06). No further intergroup differences were found even when regarding studies investigating serum, plasma, and whole blood as one group.
Results of meta-analysis: Patients with FMS have higher plasma levels of IL-6 compared to controls. The discrepancy to the results of the systematic review (higher plasma IL-8 levels in patients with FMS) is due to the fact that only few studies were suitable for meta-analysis.
Therefore the hypothesis that patients with FMS, who suffer from generalized pain may have an innate or acquired imbalance in cytokine production and secretion is plausible. Higher levels of these cytokines in plasma and/or serum of patients with FMS may be associated with pain in FMS. In line with these findings one study showed lower levels of the anti-inflammatory and analgesic cytokines IL-4 and IL-10 in FMS patients compared to healthy controls . However, it remains elusive, whether these systemic changes in cytokine levels are the cause of pain in FMS or its consequence. Longitudinal studies are needed to answer this question......The major consequence of our review is that cytokine research in FMS pathophysiology needs substantial improvement. More hypothesis-based and mechanistic studies are needed to understand if distinct cytokines are involved in causing symptoms of FMS or if they may be used as biomarkers of FMS symptomswww.biomedcentral.com/1471-2474/12/245
Is Inflammation a Mitochondrial Dysfunction-Dependent Event in Fibromyalgia?
Mario D. Cordero,1 Eduardo Díaz-Parrado,1 Angel M. Carrión,2 Simona Alfonsi,3 José Antonio Sánchez-Alcazar,4 Pedro Bullón,5 Maurizio Battino,6 and Manuel de Miguel1
Antioxidants & Redox Signaling
Fibromyalgia (FM) is a complex disorder that affects up to 5% of the general population worldwide. Both mitochondrial dysfunction and inflammation have been implicated in the pathophysiology of FM. We have investigated the possible relationship between mitochondrial dysfunction, oxidative stress, and inflammation in FM. We studied 30 women diagnosed with FM and 20 healthy women. Blood mononuclear cells (BMCs) from FM patients showed reduced level of coenzyme Q10 (CoQ10) and mtDNA contents and high level of mitochondrial reactive oxygen species (ROS) and serum tumor necrosis factor (TNF)-alpha [an inflammatory cytokine] and transcript
levels. A significant negative correlation between CoQ10 and TNF-alpha levels (r=−0.588; p<0.01), and a positive correlation between ROS and TNF-alpha levels (r=0.791; p<0.001) were observed accompanied by a significant correlation of visual analogical scale with serum TNF-alpha and transcript
levels (r=0.4507; p<0.05 and r=0.7089; p<0.001, respectively). TNF-alpha release was observed in an in vitro (BMCs) and in vivo (mice) CoQ10 deficiency model. Oral CoQ10 supplementation restored biochemical parameters and induced a significant improvement in clinical symptoms (p<0.001). These results lead to the hypothesis that inflammation could be a mitochondrial dysfunction-dependent event implicated in the pathophysiology of FM in several patients indicating at mitochondria as a possible new therapeutic target. Antioxid. Redox Signal. 00, 000–000.
There was a 2003 Egyptian study, in which IL-6 and IL-8 ( an inflammatory marker) were looked at: applications.emro.who.int/imemrf/egypt_rheum_regabil_2003_30_5_889.pdf.
That study also felt that IL -6 may be related to fatigue and sleep issues.
This study is an interesting and different finding, from 2009ebm.rsmjournals.com/content/234/2/232.full
This found many interesting correlations and fluctuations, but here are quotes which include IL-6, and also IL-10.
"We interpret this to indicate a skew away from the normal balance favoring pro-inflammatory cytokines in controls toward one favoring an anti-inflammatory response in FM. These changes toward anti-inflammatory predominance in FM may explain their common complaint of disturbed sleep because these cytokines are known to disrupt sleep."
"..we now report that statistical evaluation of cytokine levels over time reveals patterns that are relatively quiescent and then interrupted by relatively large increases, consistent with episodic secretion.....The cytokine findings in patients with FM differed from those of healthy controls—primarily in nighttime, a time that has not been previously studied in this illness group. Healthy controls but not patients showed nocturnal correlations between IL-10 and IL-1βand TNF-α. In the same vein, healthy subjects showed daytime correlations between IL-10 and IL-6 which were not seen in FM. These correlations suggest an interaction among these cytokines, perhaps in regulating normal sleep; the fact that these correlations did not extend to the nighttime for IL-6 may reflect the fact that it is more pro-inflammatory than soporific"
----- ----- -----doctorstevesbanjo.com/novel-theory-fibromyalgia/
This link above is footnoted, it discusses pro-inflammatory cytokine excess.
Some use Low Dose Naltrexone (LDN) to reduce unhealthy inflammation:
Recent studies have determined that ultra low doses of naltrexone have demonstrated attenuation of proinflammatory cytokines and neurotoxic superoxides by suppressive effects on microglia cells found in the CNS. Erythrocyte sedimentation rate (ESR) may be an identifying marker for a fibromyalgia subgroup, those with concomitant systemic inflammation, has demonstrated a more than 80% response to LDN therapy. cme.dannemiller.com/painstracts/activity.cfm?d=9-01- 2009&m=2&abstract=10
LDN research pilot study 2009 Jarred Younger PhD and Sean Mackey MD & PhDwww.ncbi.nlm.nih.gov/pmc/articles/PMC2891387/
When Younger, Parkitney and MacLain published results of the 2009 and their larger 2012 LDN/fibro studies in a rheumatology journal in 2014, they wrote that even peripheral inflammation was reduced.
J Rheumatol. 2004 Oct;31(10):2082-5.www.ncbi.nlm.nih.gov/pubmed/15468381
Alpha1-antitrypsin replacement therapy controls fibromyalgia symptoms in 2 patients with PI ZZ alpha1-antitrypsin deficiency.
"Two Spanish sisters with alpha1-antitrypsin (AAT) deficiency and fibromyalgia (FM) started AAT replacement therapy with commercial alpha1-antitrypsin infusions in 1992. They both experienced a rapid, progressive, and constant control of their FM symptoms during the next 6 years (1992-98). However, in 1998, treatment of both patients was affected by the worldwide commercial shortage of AAT replacement therapy; replacement therapy infusions were halted for about
4-6 consecutive months every year for 5 years. As a result, we observed a striking recurrence of FM symptoms. Equally striking was the total disappearance of these symptoms when AAT replacement therapy infusions were resumed.
" In recent studies abnormal profiles of inflammation markers in serum and biopsies have been found in FM patients. Since most of these inflammation mediators can be inhibited by AAT, these observations would suggest that at least a subset of the FM syndrome could be related to an inflammatory process, possibly due to an imbalance between inflammatory and anti-inflammatory substances, in the soft body tissues. "
"Future directions of research would be: (1) to develop epidemiological studies to determine the gene frequency of AAT deficiency alleles in FM patients; (2) implementation of a double-blind placebo-controlled clinical trial to determine the specific role of AAT augmentation therapy in AAT-D patients with FM; (3) identification of specific laboratory markers for diagnostic and clinical evaluation purposes in FM; (4) application of the newest medical imaging techniques for diagnosis; and (5) identification of genetic, familial, and environmental risk factors suspected to participate in the FM syndrome development. "
by Blanco et al.
Titled alpha1-Antitrypsin and fibromyalgia: new data in favour of the inflammatory hypothesis of fibromyalgia.)
Bote ME, García JJ, Hinchado MD, Ortega E.
Inflammatory/Stress feedback dysregulation in women with fibromyalgia.
Group of Immunophysiology, Dept of Physiology, Faculty of Sciences, University of Extremadura, Badajoz, Spain.
As well as being a pro-inflammatory cytokine, IL-8 is also considered to be an inflammatory chemokine since it is a potent chemoattractant for neutrophils  (cells essential for the development of the inflammatory response), besides being a potent promoter of sympathetic pain.
Results: FM patients showed an inflammatory state accompanied by an altered stress response. This is mainly manifested by high circulating levels of IL-8 and CRP
(in 100% of the FM group), high circulating levels of cortisol, and increased systemic levels of NA and eHsp72. There is also increased release of inflammatory cytokines (IL-1β, TNFα, IL-6, IL-10, IL-18 and MCP-1) by monocytes, and enhanced activation of the functional capacity of neutrophils (chemotactic, phagocytic and fungicidal activities). Conclusion: An inflammatory/stress feedback dysregulation underlies FM. Whether dysregulation of the stress response is the cause of the inflammatory dysregulation or vice versa is also discussed.
Published in NeuroImmunoModulation
All papers are reviewed by at least two referees.
© 2012 S. Karger AG, Baselwww.karger.com/Article/FullText/341664
Post Edited (Rockon) : 2/10/2018 3:06:49 PM (GMT-7)