Lower Levels Of Anti-inflammatory Proteins May Contribute To Chronic Widespread

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Lower Levels Of Anti-inflammatory Proteins May Contribute To Chronic

Widespread Pain

http://www.medicalnewstoday.com/medicalnews.php?newsid=48179

Chronic widespread pain, a common medical condition, can be difficult

to treat and is often associated with fatigue, poor sleep and

depression. A connection between fibromayalgia (FM) and cytokines

(proteins that act as messengers between cells) was suspected after

cancer patients treated with the cytokine interleukin -2 developed FM-

like symptoms. Since then, other studies have shown contradictory

results. A new study published in the August 2006 issue of Arthritis

& Rheumatism (http://www.interscience.wiley.com/journal/arthritis)

examined cytokine profiles in patients with chronic widespread pain

and found that they had significantly lower levels of the anti-

inflammatory cytokines IL-4 and IL-10.

Led by Nurcan Uceyler of Julius-Maximilians University in Wurzburg,

Germany, researchers analyzed cytokines in 40 patients with chronic

widespread pain (26 of whom had FM), 40 controls and an additional

group of 15 patients. The 40 pain patients had received intravenous

immunoglobulin (IVIG) as a novel treatment for pain that was not

responsive to standard therapy, while the additional 15 patients did

not receive this treatment. Blood samples were analyzed for both pro-

inflammatory and anti-inflammatory cytokines. In addition, patients

were asked to rate their pain, fatigue, mood, cognitive function and

sleep quality on a scale of 1 to 10.

Patients in the pain group did not differ in the expression of the

pro-inflammatory cytokines IL-2, IL-8 and TNF & #945;, but did have

significantly lower levels of the anti-inflammatory cytokines IL-4

and IL-10 compared with the healthy control group. The 15 patients in

the additional group showed similar findings, although the difference

in IL-10 between this group and the controls was not statistically

significant.

The authors point out that there may be several factors involved in

the cause of low cytokine levels and how they might be linked to

pain. Previous studies have shown that IL-10, administered as a

protein or via gene transfer, reduces sensitivity to pain. Similarly,

IL-4 has been shown to dull the pain response. " Signals arising

through physiologic stimulation of the opioid receptor system may be

reduced in patients with low IL-4 levels with subsequent increase in

pain perception and the common relative opioid resistance seen in

patients with chronic widespread pain, " the authors note. In

addition, genetic variations in different cytokine genes are

associated with distinct diseases, such as the association between IL-

4 gene variations and asthma, Crohn's disease, and chronic

polyarthritis. " The low levels of IL-4 and IL-10 we observed in the

patients with chronic widespread pain might therefore also be caused

by genetic alterations either in the cytokine genes themselves or in

regulatory elements, although other factors may be involved, " the

authors state.

The authors acknowledge that this study on 6 key cytokines does not

exclude the possibility that other cytokines may play a role in

chronic widespread pain. While they acknowledge that low levels of

anti-inflammatory cytokines may be a consequence of chronic

widespread pain and its treatment, they favor the hypothesis that

these proteins actually play a role in the pathophysiology of chronic

widespread pain. " Once confirmed and validated in further studies, "

they conclude, " cytokine expression patterns may eventually help in

supporting the diagnosis of chronic widespread pain and in guiding

the appropriate treatment approach. "

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Article: " Reduced Levels of Antiinflammatory Cytokines in Patients

With Chronic Widespread Pain, " Nurcan Uceyler, Regine Valenza,

Stock, Schedel, Günter Sprotte, Sommer,

Arthritis & Rheumatism, August 2006; (DOI: 10.1002/art.22026).