OVERPRODUCTION OF PROINFLAMMATORY CYTOKINES IMBALANCED BY THEIR ANTAGONISTS IN POEMS SYNDROME

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin chan ges (POEMS) syndrome is a rare multisystem disorder of obscure pathoge nesis associated with osteosclerotic myeloma. Circulating levels of pr oinflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha] inter leukin-1 beta [IL-1 beta], IL-2, IL-6, and interferon gamma [IFN gamma ]), anti-inflammatory cytokines (transforming growth factor beta(1) [T GF beta(1)], IL-4, IL-10, and IL-13), the cytokine carrier protein alp ha 2macroglobulin, IL-1 receptor antagonist (IL-1ra), soluble TNF rece ptors (sTNFr) p55 and p75, and soluble IL-6 receptor (sIL-6r) were det ermined in 15 patients with POEMS syndrome and 15 with multiple myelom a. 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 pat ients with multiple myeloma. Serum levels of IL-2, IL-4, IL-10, IL-13, IFN gamma, alpha 2macroglobulin, and sIL-6r were similar in both grou ps. IL-1ra and sTNFrs were increased in POEMS syndrome, but out of pro portion to the increase of IL-1 beta and TNF-alpha. Serial evaluations in 1 patient showed that proinflammatory cytokine serum levels parall eled disease activity assessed by platelet count and neurologic involv ement. Our results suggest that the manifestations of POEMS syndrome m ight be regarded as the result of a marked activation of the proinflam matory cytokine network (IL-1 beta, IL-6, and TNF-alpha) associated wi th a weak or even decreased (TGF beta 1) antagonistic reaction insuffi cient to counteract the noxious effects of cytokines. (C) 1996 by The American Society of Hematology.