IL-18 in autoimmunity: review.
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.
Boraschi
Diana
D
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. diana.boraschi@itb.cnr.it
Dinarello
Charles A
CA
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D006801:Humans; D020382:Interleukin-18 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008954:Models, Biological; D053724:Receptors, Interleukin-18 / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
D020382:Interleukin-18; D053724:Receptors, Interleukin-18; D051193:Toll-Like Receptors