The Complexity of Cytokine Treatment in Ongoing EAE Induced with MBP Peptide 68–86 in Lewis Rats

IL-10 and TGF-β1 are important immunoregulatory cytokines associated with clinical remissions in multiple sclerosis and amelioration of experimental allergic encephalomyelitis (EAE). IL-10 and TGF-β1 have previously been shown to prevent the development of EAE. Here, we study effects of IL-10 and TGF-β1 in ongoing EAE. When IL-10 or TGF-β1 was administered by the nasal route from day 0 to day 7 postimmunization (pi), both IL-10 and TGF-β1 prevented the development of acute EAE in Lewis rats. When IL-10 or TGF-β1 was administered by the nasal route from day 5 to day 12 pi, both IL-10 and TGF-β1 failed to influence clinical EAE. The inhibition of clinical EAE severity in IL-10-prevented rats was associated with reduced proliferation, IFN-γ mRNA expression, and IFN-γ secretion, while proliferation as well as IFN-γ mRNA expression and secretion were augmented in TGF-β1-prevented rats. TGF-β1-prevented rats exhibited high levels of NO production by DC, which may mediate apoptosis of CD4+ T cells and of the DC themselves. For prevention, both IL-10 and TGF-β1 inhibited infiltration of CD4+ T cells within the CNS, but neither IL-10 nor TGF-β1 induced immune deviation from Th1 to Th2. Expression of IL-4 mRNA was not altered in IL-10- and TGF-β1-prevented rats. These results demonstrate that IL-10 and TGF-β administration by the nasal route can prevent the development of acute EAE, but by different mechanisms. The findings in rats with ongoing EAE have implications for the clinical application of cytokine treatment in autoimmune diseases.