The cytokine storm in multiple sclerosis

Abstract

MS is associated with a cytokine storm characterized by the parallel upregulation of proinflammatory (IFN-g, TNF-a, and b, and IL-12) and immune response-down-regulating (TGF-b, 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 indiviual patient. Few correlations have been observed between cytokines and clinical MS variables, though upregulation of TGF-b 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.

Keywords

cytokines perforin transforming growth factor-beta cerebrospinal fluid in situ hybridization multiple sclerosis

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References

Diab A et al. (1997) High IL-6 and low IL-10 in the CNS is associated with chronic EAE in Lewis rats . J Neuropathol Exp Neurol. (In press).

Issazadeh S et al. (1995) Cytokine production in the CNS of Lewis rats with EAE: Dynamics of mRNA expression for IL-10, IL-12, cytolysin, TNF-a and b . J Neuroimmunol 61: 205-212 .

Kivisäkk P et al. (1997) Optic neuritis and cytokines: No relation to MRI abnormalities and oligoclonal bands . Neurology (In press)

Link J. (1994) IFN-g, IL-4 and TGF-b mRNA expression in multiple sclerosis and myasthenia gravis . Acta Neurol Scand 90, (Suppl) 158: 1-58 .

Navikas V et al. (1995) Increased mRNA expression of IL- 10 in mononuclear cells in multiple sclerosis and optic neuritis . Scand J Immunol 41: 171-178 .

Navikas V et al. (1996) Augmented expression of tumor necrosis factor-a and lymphotoxin mRNA in mono-nuclear cells in multiple sclerosis and optic neuritis . Brain 119: 213-223 .

Navikas V , Link H. (1996) Cytokines and the pathogenesis of MS . J Neurosci Res 45: 322-333 .

Panitch HS , Hirsch L , Schindler J , Johnson KP. (1987) Treatment of MS with gamma IFN: Exacerbations associated with activation of the immune system . Neurology 37: 1097-1102 .

Rieckmann P et al. (1994) Cytokine mRNA levels in mononuclear cells from patients with multiple sclerosis . Neurology 44: 1523-1526 .

10.

Scolding NJ , Jones J , Compston DAS , Morgan BP. (1990) Oligodendrocyte susceptibility to injury by T cell perforin . Immunology 70: 6-10 .

11.

Sharief MK , Hentges R. (1991) Association between tumor necrosis factor-a and disease progression in patients with multiple sclerosis . N Engl J Med 325: 467-472 .

12.

Wang W-Z et al. (1992) Myelin antigen reactive T cells in cerebrovascular diseases . Clin Exp Immunol 88: 157-162 .

13.

Xiao B-G et al. (1997) Shift from anti- to proinflammatory cytokine patterns in microglia through LPS- or IFN-g-mediated pathways . Neuroreport.(Inpress)