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Markedly upregulated serum interleukin-12 as a novel biomarker in POEMS syndrome

Objective: To systematically study abnormalities in cytokine profiles in polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, which has been increasingly recognized as a cause of demyelinating neuropathy associated with plasma cell dyscrasia and elevated serum level of vascular endothelial growth factor (VEGF). Methods: In this case-control study, we measured serum levels of 27 cytokines in patients with POEMS syndrome using a multiplex suspension array system, and compared them with those of controls. In 10 patients, serial changes after treatment were analyzed. Results: Interleukin (IL)–12 as well as VEGF levels were markedly increased (p < 0.0001) in all the patients (n = 23). Ten kinds of other proinflammatory cytokines such as IL-6 and tumor necrosis factor–α were also significantly increased in the POEMS syndrome group, but in some patients the serum levels of such cytokines remained within the normal ranges. After treatments, the IL-12 as well as VEGF levels significantly decreased with clinical improvements (p > 0.01 and p > 0.05, respectively). Conclusions: Our findings suggest that serum IL-12 is a biomarker of the disease activity in POEMS syndrome. The overproduction of IL-12, as well as VEGF, is likely to play an important role in the pathogenesis of the disorder, and could contribute to the peripheral nerve demyelination in POEMS syndrome.