The cytokine storm in multiple sclerosis.

MS is associated with a cytokine storm characterized by the parallel upregulation of proinflammatory (IFN-gamma, TNF-alpha, and beta, and IL-12) and immune response-down-regulating (TGF-beta, IL-10) cytokines. Also IL-6 and the cytolytic molecule perforin are upregulated. Even when evaluated in individual MS patients over the disease course, no Th1/Th2 dichotomy is obvious but, instead, upregulation of Th1 + Th2 + Th3 cytokines simultaneously, probably reflecting the complex pathology of MS in lesion size, time and distribution in the individual patient. Few correlations have been observed between cytokines and clinical MS variables, though upregulation of TGF-beta seems to correlate with benign course and minor disability. Both pro- and antiinflammatory cytokines are also produced by microglia and astrocytes, constituting a CNS-cytokine network that interacts with the cytokine network of the immune system. This complexity is to be kept in mind when searching for cytokine abnormalities in MS.