Interleukin-18: recent advances.
OBJECTIVE
Interleukin-18 (IL-18) has potent immunomodulatory effects. It is the only cytokine with a unique capacity to induce T helper 1 or T helper 2 polarization, depending on the immunologic context. Serum levels of IL-18 are increased in many human diseases and it has been implicated in the pathogenesis of several immune-mediated processes. Some of the recent key advances in the immunobiology of IL-18 are discussed in this review.


RESULTS
Recent data from several laboratories have shed light on the structure of IL-18; the signaling cascades that are initiated; and its role on modulating T cells, dendritic cells, and natural killer cell function. Several new reports have expanded and delineated the role of IL-18 in a multitude of diseases, but only recent advances in the role of IL-18 in three disease processes (acute graft-versus-host disease, insulin-dependent diabetes, and sepsis), where it appears to play paradoxic roles are discussed.


CONCLUSIONS
Although emerging data shed more light on the complex role of IL-18 in immune reactions, they also pose more questions. Given the pleiotropic, complex, and at times paradoxic effects of IL-18 in various disease processes, better understanding of its immunobiology might lead to the development of IL-18 and/or its antagonists as therapeutic agents against immune-mediated diseases.
Reddy
Pavan
P
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0942, USA. reddypr@umich.edu
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology*; D018805:Sepsis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D020382:Interleukin-18