Verhandelingen - Koninklijke Academie voor Geneeskunde van België vol:60 issue:4 pages:271-85
Autoimmune diseases originate from a rupture in physiological immune tolerance towards self antigens. However, the formation of autoantibodies and autoreactive inflammatory cells is also regulated by the cytokine network, in which interferon-gamma (IFN-gamma), produced by NK and T lymphocytes, occupies a central position. IFN-gamma influences the function of all cell types involved in immune-mediated inflammatory reactions: antigen-presenting cells, cytotoxic and regulatory T lymphocytes, antibody-producing B lymphocytes, endothelial cells and mononuclear phagocytes. Experimental manipulations which affect the production or action of IFN-gamma invariably affect the course of experimentally induced autoimmune diseases in animals, but do so in divergent directions. A current explanatory framework for these actions of IFN-gamma invokes the T helper-1/T helper-2 (Th1/Th2) concept. According to this concept, autoimmune diseases, like other immune reactions, fall apart in two categories depending on whether the T helper lymphocytes assume a Th1 or Th2 profile. IFN-gamma is assumed to fulfill the function of a promotor and effector of the Th1 profile and is associated with inflammation and tissue damage typical for cell-mediated hypersensitivity reactions. Accordingly, IFN-gamma should boost autoimmune diseases of the Th1 type. However, experimental testing of this prediction contradicts this implication and necessitates revision of the function assigned to IFN-gamma in the Th1/Th2 concept.