On cytokines, inflammation, pain and fibromyalgia
Cytokines are inter-cellular chemical messengers produced mostly by white blood cells. Some are generally pro-inflammatory (inflammatory cytokines turn inflammation ‘on’) while others are generally anti-inflammatory (they turn inflammation ‘off’). High levels of inflammatory cytokines indicate an ongoing inflammatory process. There might not be the appearance of ‘inflammation’ as we generally think of it – but there is a ‘type’ of inflammation at work – the ‘inflammatory response system’ is active – the process of inflammation has begun.
The primary study referenced below is important because it provides good evidence that inflammation (inflammatory cytokines, or the inflammatory response system) plays a significant role in fibromyalgia.
Specifically, circulating levels of IL-8 (a pro-inflammatory cytokine) were found to be elevated in those with fibromyalgia. That’s important, but what’s more significant is that the severity of pain was observed to correlate with the level of IL-8. That is, when there was more IL-8 there was more pain. When there was less IL-8 there was less pain. Does IL-8 cause the diffuse pain of fibromyalgia? Let’s see.
Inflammatory cytokine IL-8 seems to play an important role in fibromyalgia.
In the study summarized below, 20 fibromyalgia patients and 80 healthy controls were monitored over the course of six months. Circulating levels of various ‘markers’ of inflammation (inflammatory cytokines IL-6, IL-8 and TNF, as well as anti-inflammatory cytokines IL-4 and IL-10) were evaluated over time. Any changes in response to therapy were noted.
At the beginning of the study, before any treatment was administered, fibromyalgia patients were found to have substantially higher than normal levels of IL-8 and TNF (tumor necrosis factor – another inflammatory cytokine.) No other cytokine differences were observed.
Once treatment was initiated (multi-modal therapy including oral pain medications) the level of TNF quickly decreased to normal – within 10 days. But the decrease in TNF had no impact on pain. TNF dropped but pain remained high. So the inflammatory cytokine TNF may not be all that important in fibromyalgia – at least not as a direct cause of pain. (IL-8 levels were unchanged at this point.)
What happened next?
Over the remaining 6 months of therapy, IL-8 decreased in most patients, but only by a little, and only very slowly. At the end of six months most patients still had relatively high levels of both IL-8 and pain.
But a few patients had a much more substantial decrease in their IL-8 level. What happened to them?
Those patients with significantly lower IL-8 at the end of the study also had significantly less pain!
Not only that, but it turns out those with the highest levels of IL-8 at the end of the study also had the most pain.
How closely did pain severity track with IL-8? Well, a perfect correlation (as these things are defined) would be 1.0. The actual correlation in this study was 0.78 – which is very high. That suggests a strong link between IL-8 and pain.
Circulating cytokine levels compared to pain in patients with fibromyalgia — a prospective longitudinal study over 6 months.
Summary of the abstract
This prospective study examined circulating cytokines in patients with fibromyalgia over six months. Correlations between serum cytokine concentrations and pain intensity were investigated in fibromyalgia patients undergoing multi-disciplinarytherapy.
On admission, fibromyalgia patients had elevated levels of IL-8 and TNF, but not IL-6.
There were no significant differences observed in fibromyalgia patients for circulating levels of IL-4 or IL-10.
High IL-8 levels remained consistent during the followup, but within 10 days, TNF levels returned to normal.
After 6 months of treatment, IL-8 levels were significantly lower, but remained elevated relative to healthy controls.
IL-8 but not TNF blood levels were found to correlate with pain intensity in fibromyalgia patients.
These results suggest the importance of IL-8 in fibromyalgia.