Abstract
We report that N-acetyl-L-cysteine (NAC) treatment blocked induction of TNF-α, IL-1β, IFN-γ and iNOS in the CNS and attenuated clinical disease in the myelin basic protein induced model of experimental allergic encephalomyelitis (EAE) in Lewis rats. Infiltration of mononuclear cells into the CNS and induction of inflammatory cytokines and iNOS in multiple sclerosis (MS) and EAE have been implicated in subsequent disease progression and pathogenesis. To understand the mechanism of efficacy of NAC against EAE, we examined its effect on the production of cytokines and the infiltration of inflammatory cells into the CNS. NAC treatment attenuated the transmigration of mononuclear cells thereby lessening the neuroinflammatory disease. Splenocytes from NAC-treated EAE animals showed reduced IFN-γ production, a Th1 cytokine and increased IL-10 production, an anti-inflammatory cytokine. Further, splenocytes from NAC-treated EAE animals also showed decreased nitrite production when stimulated in vitro by LPS. These observations indicate that NAC treatment may be of therapeutic value in MS against the inflammatory disease process associated with the infiltration of activated mononuclear cells into the CNS.
Highlights
Multiple sclerosis (MS) is a chronic demyelinating disease marked by focal destruction of myelin, resulting in the loss of oligodendrocytes and axons accompanied by an inflammatory disease process [1,2,3]
Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. Both MS and EAE are initiated by a T-cell mediated autoimmune response (CD4+ and CD8+) against myelin components followed by induction of inflammatory mediators that in turn define the pattern of perivascular migration of activated T-cells and mononuclear cells into the CNS [1,2,3,4]
Animals induced for EAE but given only the vehicle closely followed the disease progression of MBPtreated rats
Summary
Multiple sclerosis (MS) is a chronic demyelinating disease marked by focal destruction of myelin, resulting in the loss of oligodendrocytes and axons accompanied by an inflammatory disease process [1,2,3]. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS. Both MS and EAE are initiated by a T-cell mediated autoimmune response (CD4+ and CD8+) against myelin components followed by induction of inflammatory mediators (chemokines and cytokines) that in turn define the pattern of perivascular migration of activated T-cells and mononuclear cells into the CNS [1,2,3,4]. The sequence of events associated with loss of oligodendrocytes and myelin in MS and EAE are not precisely understood.
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