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Abstract ObjectiveTo delineate the possible implication of the immunosuppressive cytokine transforming growth factor beta 1 (TGF-β1) in the pathogenesis of Guillain-Barré syndrome. Guillain-Barré syndrome is a disorder that may implicate cytokines in its pathogenesis. TGF-β1 is a potent anti-inflammatory cytokine occasionally shown to be regulated in the course of demyelinating disorders. MethodsThe study measured circulating proinflammatory and anti-inflammatory cytokines from the progressing phase to early recovery in patients with Guillain-Barré syndrome. Plasma concentrations of TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, and TGF-β1 were prospectively evaluated in 15 patients with Guillain-Barré syndrome every three days for the first 15 days after admission to hospital, and in 15 controls with non-inflammatory neurological diseases. ResultsConcentrations of TGF-β1 in plasma were decreased in 13/15 patients (87 %) at day 1, remained low during progression and the plateau of paralysis (days 1–10), and then progressively increased up to control concentrations during early recovery (days 12–15). Concentrations of plasma TGF-β1 correlated positively with motor function, the lowest values being found in the most disabled patients. Concentrations of plasma TGF-β1 were decreased before any treatment, and during treatment by either plasma exchange or intravenous immunoglobulins, plasma exchange being associated with a more pronounced decrease in TGF-β1 at day 7. Circulating TNF-α concentrations were raised, as previously reported, when other cytokines were either randomly increased (IL-2, IL-6), or undetectable (IL-1, IL-4, IL-7, IL-10). ConclusionsDown regulation of TGF-β1 in the early course of Guillain-Barré syndrome could participate in neural inflammation.

To evaluate a possible implication of cytokines in the pathogenesis of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, we studied five consecutive patients with this condition, of which four had sclerotic bone lesions and four had multicentric Castleman's disease. Interleukin-1 beta (IL-1 beta) and IL- 6 serum levels were determined in these patients (13 serum samples) and in patients with multiple myeloma (5) and Waldenstrom's macroglobulinemia (5). In situ hybridization of the relevant mRNAs was performed on lymph node specimens of two patients with POEMS syndrome who had Castleman's disease. Elevated serum levels of IL-1 beta (13/13 samples), and IL-6 (7/13 samples) were found in patients with POEMS syndrome. In the other patients, serum IL-1 beta was undetectable or slightly increased and IL-6 was elevated in a single patient with Waldenstrom's macroglobulinemia. Abundant IL-1 beta mRNA-producing cells were present in interfollicular spaces in the two tested patients, while IL-6 mRNA-producing cells were rare. We conclude that IL-1 beta and IL-6 serum levels may be chronically elevated in patients with POEMS syndrome, and that lymph node may be one site of IL-1 beta overproduction. These results are in keeping with the hypothesis that cytokines mediate systemic manifestations of POEMS syndrome.

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystem disorder of obscure pathogenesis associated with osteosclerotic myeloma. Circulating levels of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) interleukin-1 beta [IL-1 beta], IL-2, IL-6, and interferon-gamma [IFN- gamma]), anti-inflammatory cytokines (transforming growth factor beta 1 [TGF beta 1], IL-4, IL-10, and IL-13), the cytokine carrier protein alpha 2 macroglobulin, IL-1 receptor antagonist (IL-1ra), soluble TNF receptors (sTNFr) p55 and p75, and soluble IL-6 receptor (sIL-6r) were determined in 15 patients with POEMS syndrome and 15 with multiple myeloma. Patients with POEMS syndrome had higher serum levels of IL-1 beta, TNF-alpha, and IL-6 and lower serum levels of TGF beta 1 than did patients with multiple myeloma. Serum levels of IL-2, IL-4, IL-10, IL- 13, IFN-gamma, alpha 2 macroglobulin, and sIL-6r were similar in both groups. IL-1ra and sTNFrs were increased in POEMS syndrome, but out of proportion to the increase of IL-1 beta and TNF-alpha. Serial evaluations in 1 patient showed that proinflammatory cytokine serum levels paralleled disease activity assessed by platelet count and neurologic involvement. Our results suggest that the manifestations of POEMS syndrome might be regarded as the result of a marked activation of the proinflammatory cytokine network (IL-1 beta, IL-6, and TNF- alpha) associated with a weak or even decreased (TGF beta 1) antagonistic reaction insufficient to counteract the noxious effects of cytokines.

An unusual inflammatory myopathy characterised by an infiltration of non-epithelioid histiocytic cells has been recorded with increasing frequency in the past 5 years in France. We reassessed some of these cases.