John Libbey Eurotext

European Cytokine Network


IL-18 in autoimmunity: review Volume 17, numéro 4, December 2006

Laboratory of Cytokines, Unit of Immunobiology, Institute of Biomedical Technologies, National Research Council, CNR, Area della Ricerca di S. Cataldo, via G. Moruzzi 1, I-56124 Pisa, Italy, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, CO 80262, USA

IL-18 is among the cytokines responsible for immune-mediated pathologies and is probably one of the factors that contribute to the pathogenesis of autoimmune diseases. Identification of the causes of uncontrolled IL-18 production and activity in autoimmunity would allow for novel therapeutic targets to effectively block autoimmune activation and inhibit concomitant tissue damage. IL-18 is produced mainly by monocytes/macrophages in response to stimuli of viral/bacterial origin, its production being therefore one of the effects of innate immunity initiated by host-pathogen interaction. In this review, we summarise the evidence supporting both the effector and the pathogenic role of IL-18 in autoimmunity, and propose that the disturbed mechanism of innate immunity, resulting from macrophage activation through innate immunity receptors (TLR/IL-1R family), may be the basis of pathologically high levels of IL-18 production and activation. Unravelling the mechanisms of IL-18 production and activity in autoimmune diseases will allow the identification of targets for more effective therapeutic intervention.