**2. Case (should have been previously) closed**

Face validity favoring a major pathogenic role for cytokine-mediated inflammation in FMS has been addressed in the past. Although initial reports of intermuscular fibrous tissue inflammation by Stockman led Gowers to name the condition "fibrositis," [5, 6], contemporary light and magnetic resonance imaging histological reports showed no evidence for peripheral muscle inflammation [7, 8]. These data should have closed the book on inflammation as a prominent etiopathogenic mechanism in FMS. Then along came inflammatory mediators.

In some contemporary reviews of FMS pathogenesis, inflammation is referenced in passing, as it is in these three chapters [9]. Whether this is done for "completeness," after all, FMS is

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often misclassified as a "connective tissue disease" (a misnomer), most of which are inflammatory in nature, or that such reference adds a sort of "scientific patina" to the discussion is unclear.

The third review of 12 separate analyses reported increased inflammatory cytokines IL-1ra, IL-6, and IL-8, and anti-inflammatory interleukin-10 (IL-10) or low anti-inflammatory interleukin-4 (IL-4) and IL-10 [24]. Among the inflammatory chemokines also linked to signs and symptoms, monocyte chemoattractant protein-1 (MCP-1), eotaxin among others, were elevated. Two potentially innovative separate controlled analyses described cytokine and chemokine concentrations in the supernatant after mitogen stimulation of cultured monocytes, using a logistical regression model to achieve statistically determined weighting for each chemokine and cytokine, and offered this score as diagnostic test for FMS [30, 31]. Of interest, the inflammatory cytokines and chemokines including IL-6 were lower in concentration compared to healthy controls or individuals with autoimmune disease. These findings suggest increased damping control of inflammation in FMS. The authors of both these studies, however, failed to determine

Introductory Chapter: A Challenge to the Concept that Inflammation Plays a Prominent…

http://dx.doi.org/10.5772/intechopen.72936

3

the prevalence of depression or analyze its potential effects on cytokine concentrations.

through sympathetic nervous system mechanisms [32].

healthy control patients.

**5. Depression and inflammation**

trol for depression. This is an unfortunate omission.

although inconsistencies were common [26].

Among the most novel analyses was a report of elevation of intrathecal IL-8 derived from glia cells supporting the hypothesis that FMS symptoms might be mediated by glial cell activation

In summary, in individuals with FMS, peripheral blood IL-6, IL-1ra, and IL-8 concentrations may be a bit higher and IL-4 and IL-10 lower, and IL-8 may be relatively higher in the cerebral spinal fluid than in healthy controls. Inflammatory chemokines may also be higher than in

Depression and FMS are very often comorbid and show a bidirectional association [19, 33–38]. The prevalence of depression in FMS has been estimated to range from 20 to 80% in a detailed review [39]. Furthermore, the severity of comorbid depression correlates with FMS severity measures [40–42]. We have reported that depression, with a 73% prevalence, correlated better with core FMS symptoms than did any other variable in a cohort of 305 FMS patients [43].

As in FMS, similar mild elevation of CRP and inflammatory cytokines and chemokines have been demonstrated in depressed individuals in controlled analyses [44–53]. Many primary analyses of FMS inflammation [15, 30, 31, 54–56] and reviews [23, 28], however, failed to con-

Maes and colleagues evaluated the serum concentrations of inflammatory cytokines in rela-

Serum soluble gp130, an important inflammatory cytokine signal transducer, and a soluble interleukin-6 receptor, Il-1 ra, were significantly higher in FMS patients with a Hamilton Depression Rating Scale score >16 than in FMS patients with scores of 16 or lower or in healthy controls. In the opinion of the Menzies' integrated review, which included the Maes analysis, higher inflammatory cytokines in FMS, including IL6, were related to the degree of depression,

tionship to depression among 21 FMS patients compared to 33 healthy controls [57].

This review examines the validity of the concept that cytokine- and chemokine-driven inflammation is relevant to the pathogenesis of FMS.
