Critical influences of the cytokine orchestration on the outcome of myelin antigen-specific T-cell autoimmunity in experimental autoimmune encephalomyelitis and multiple sclerosis

Abstract

In EAE/MS, effector molecules are produced as a result of the interaction between T lymphocytes and antigen-presenting cells and the spectrum of cytokines produced is likely to decisively influence the disease outcome. These events may be more important, or at least more easily accessible to therapeutic intervention, than particular autoantigen specificities. Data from EAE suggest that cytokines connected to the Th1 phenotype of lymphocytes, especially IFN-gamma but also TNF-beta, TNF-alpha and IL-12, may promote inflammation while cytokines connected to the Th2 subset, IL-4, IL-10 and TGF-beta, may potentially have a role in disease limitation. It will be important to accurately study cytokines during immunotherapeutic interventions and in relation to immunogenetic variables in order to aim at immunotherapeutically intervening in the Th1, Th2 balance as well as counteracting disease-promoting cytokines such as IFN-gamma and TNF-alpha or promoting the action of downregulatory cytokines such as IL-10 and TGF-beta.