Modulation of susceptibility and resistance to an autoimmune model of multiple sclerosis in prototypically susceptible and resistant strains by neutralization of interleukin-12 and interleukin-4, respectively

Experimental autoimmune encephalomyelitis (EAE), an animal model for multip le sclerosis, is mediated by Th1 cells. The major Th1 inducer, IL-12, enhan ces EAE, while its blockade suppresses it. IL-4 suppresses EAE. Here, we de termined IFN-gamma and IL-4 production by myelin basic protein-stimulated l ymphocytes from prototypically EAE-susceptible SJL/J and EAE-resistant BALB /c mice, 9 days after immunization with spinal cord homogenate, While lymph ocytes from SJL/J mice produce IFN-gamma and no IL-4, lymphocytes from BALB /c mice produce IL-4 and no IFN-gamma. Since early endogenous production of IL-12/IFN-gamma or IL-4 is linked to Th1 or Th2 responses, respectively, w e determined whether neutralization of IL-12 or IL-4 at immunization modifi es susceptibility or resistance to EAE, SJL/J mice given neutralizing anti- IL-12 mAb are protected from EAE. BALB/c mice given neutralizing anti-IL-1 mAb develop EAE, while those treated with control antibody remain resistant . These studies confirm the pivotal role of IL-12 in EAE development and sh ow that endogenous IL-4 is important for determining the genetic resistance to EAE. (C) 2000 Academic Press.