Acceleration of experimental autoimmune encephalomyelitis in interleukin-10-deficient mice: Roles of interleukin-10 in disease progression and recovery

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) which is often used as an animal model for human multiple sclerosis (MS). The disease is mediated by autoreactive lymphocytes recognizing myelin self-antigens. The autoreactive lymphocytes elicit autoimmune inflammation in the CNS and lead to demyelination and loss of neurological functions. Although autoimmune encephalomyelitis can lead to irreversible nervous tissue injury and demise of animals, EAE is often characterized by spontaneous disease recovery or remission. It is not known how EAE progression is regulated, nor is it clear how autoimmune inflammation in the CNS can resolve while the myelin-specific lymphocytes and myelin self-antigens remain in the animals. Cytokines, especially TH2-type cytokines, have long been suggested to play a role in regulating EAE. However, experiments using recombinant cytokines or neutralizing antibodies to cytokines have generated conflicting results. To determine the roles of interleukin (IL)-4 and IL-10 in experimental autoimmune encephalomyelitis, we have studied mice deficient in IL.4 or IL- 10. We found that IL.10- but not IL-4-deficient mice had accelerated EAE following immunization with myelin oligodendrocyte glycoprotein (MOG). Importantly, spontaneous recovery from EAE occurred in normal and IL-4- deficient mice, but not in mice deficient in IL-10. Furthermore, we established that the acceleration of EAE in IL-10-deficient mice was associated with a decrease in IL-4 and an increase in IFN-γ production in response to MOG antigen. These results strongly suggest that IL-10 plays a crucial role in the progression and recovery of autoimmune encephalomyelitis.