IL-4 ABROGATES THE INHIBITORY EFFECT OF IL-10 ON THE DEVELOPMENT OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN SJL MICE

IL-10 and IL-4 were studied with respect to their capacity to inhibit experimental allergic encephalomyelitis (EAE) induced in SJL/J mice by immunization with the proteolipid protein peptide PLP139-151. Treatme nt with 2 mu g IL-10/day from day 0 until day 12 delayed onset of dise ase and inhibited the severity of EAE, By contrast, a daily dose of 0. 5 mu g IL-4 was ineffective. Instead of acting in a synergistic fashio n, IL-4 even abrogated the inhibitory effect of IL-10, The effects of IL-10 and IL-4 treatment were largely consistent with the (lack of) ab ility of these cytokines to down-regulate the inflammatory response in brain tissue, Although IL-4 was ineffective in the inhibition of EAE, lymph node cells from IL-4-treated mice displayed a strongly inhibite d peptide-specific IFN-gamma production. By contrast, IL-10, which was effective in inhibiting EAE, showed no significant inhibition of IFN- gamma at this level, Neither cytokine treatment resulted in detectable levels of peptide-specific IL-4. Indirect evidence for the activity o f T(h)2 cells in vivo came from the observation that IL-10 inhibited t he primary PLP139-151-specific IgG2a and IgG3 response in favor of IgG 1, whereas IL-4 inhibited the primary antibody response to the peptide , regardless of subclass, The combination of IL-4 and IL-10 did not af fect the subclass composition, The observation that IL-10-treated mice remained sensitive to re-induction of EAE is not in support of an imp ortant role of T(h)2 cells in regulating disease activity in this mode l of actively induced EAE.