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Overproduction of proinflammatory cytokines imbalanced by their antagonists
in POEMS syndrome
RK Gherardi, L Belec, M Soubrier, D Malapert, M Zuber, JP Viard, L Intrator, JD Degos and FJ Authier
Groupe d'Etude et de Recherche sur le Nerf le Muscle, GERMEN, Faculte de
Medecine de Creteil-Paris XII, Paris, France.
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.
Volume 87,
Issue 4,
pp. 1458-1465,
02/15/1996
Copyright © 1996 by The American Society of Hematology
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