The Inflammation Component in FM - more Correlations with CFS/POTS

Cort

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Inflammatory disorder? Yes! Just as in (some studies) in CFS we have increased levels of two pro-inflammatory cytokines; TNF-a and IL-8. Why are they interested in ADMA? Increased ADMA is found in type II diabetes and metabolic syndrome - two inflammatory conditions and the endothelial cells that line our blood vessels play a key role in inflammation. THey are implicated in atherosclerosis and heart disease.

A MERUK study brought up disturbing questions about cardiovascular system functioning in CFS. They found high levels of the type of oxidants that contribute to these types of problems. Now, it appears they are present in FM as well.
This appears to be evidence that inflammation and, in particular, vascular dysfunction, is present in these types of disorders.

http://www.ncbi.nlm.nih.gov/pubmed/21291875

Clin Biochem. 2011 Jan 31. [Epub ahead of print]
Asymmetric dimethylarginine (ADMA) levels are increased in patients with fibromyalgia: Correlation with Tumor necrosis factor-α (TNF-α) and 8-iso-Prostaglandin F(2α) (8-iso-PGF(2α)).

Topal G, Donmez A, Uydes Doğan BS, Kucur M, Taspinar Cengiz D, Berkoz FB, Erdogan N.
Department of Pharmacology, Istanbul University, Faculty of Pharmacy, 34116, Beyazit, Istanbul, Turkey.
Abstract

Objective The aim of the study was to investigate serum levels of asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and plasma levels of 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)) in patients with fibromyalgia. Design and method 27 patients with fibromyalgia and 20 healthy controls were enrolled in this study. ADMA, TNF-α, IL-6 and 8-iso-PGF(2α), levels were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS: Serum levels of ADMA and TNF-α and plasma levels 8-iso-PGF(2α) were significantly increased in patients with fibromyalgia compared to controls. However, no significant difference was observed in IL-6 levels between the two groups. ADMA concentrations were positively correlated with TNF-α and 8-iso-PGF(2α) levels in patients with fibromyalgia.

CONCLUSION: This is the first study reporting that ADMA levels are significantly elevated in patients with fibromyalgia in association with increased 8-iso-PGF(2α) and TNF-α concentrations. Thereby, ADMA could be suggested as a reliable marker of endothelial dysfunction in patients with fibromyalgia.
Copyright 2010. Published by Elsevier Inc.

ADMA - But there is an even bigger link. ADMA
is closely related to L-arginine. If ADMA levels are up they l-arngine will not be able to produce nitric oxide, "a key chemical involved in normal endothelial function and, by extension, cardiovascular health."

ADMA/NO/POTS connection - what is the NO connection in CFS? Stewart believe low nitric oxide levels play a key role in the postural tachycardia syndrome (POTS) and he has big NIH grant to study it.

From Stewart's Study - Data suggest the involvement of nitric oxide (no) and angiotensin in producing redistributive hypovolemia and sympathoexcitation. The overall objective of the application is to define mechanisms of CFS/POTS related to bioavailable no, and to explore the subclinical microvascular abnormalities in CFS without POTS (CFS/~POTS).
It looks like CFS researchers should be looking for ADMA as well - and linking that to low NO, inflammation, vascular problems and POTS. Of course there is the low blood flow issue as well - lots of interesting avenues in the vascular systems of CFS (and perhaps FM)

I love it when these fields and groups come together because they should each be feeding off each - and prompting new insights in the others. (Why we need an NEID Institute)
 

Enid

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Lovely when they all come together (exposing too all the Pathology - multi system). It's a joy to read you.
 

Emootje

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I would like to add another connection:
The isoprostane [8-iso-PGF(2α)]/Endothelin-1/Atrial Natriuretic Peptide/Low Blood Volume/POTS connection.
I hope Stewart would consider researching ANP as causal factor of orthostatic intolerance in CFS and FM.