Interleukin-18 regulates both TH1 and TH2 responses

Citation
K. Nakanishi et al., Interleukin-18 regulates both TH1 and TH2 responses, ANN R IMMUN, 19, 2001, pp. 423-474
Citations number
291
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Immunology
Journal title
ANNUAL REVIEW OF IMMUNOLOGY
ISSN journal
0732-0582 → ACNP
Volume
19
Year of publication
2001
Pages
423 - 474
Database
ISI
SICI code
0732-0582(2001)19:<423:IRBTAT>2.0.ZU;2-9
Abstract
Although interleukin-18 is structurally homologous to IL-1 and its receptor belongs to the IL-1R/Toll-like receptor (TLR) superfamily, its function is quite different from that of IL-1. IL-18 is produced not only by types of immune cells but also by non-immune cells. In collaboration with IL-12, IL- 18 stimulates Th1-mediated immune responses, which play a critical role in the host defense against infection with intracellular microbes through the induction of IFN-gamma. However, the overproduction of IL-12 and IL-18 indu ces severe inflammatory disorders, suggesting that IL-18 is a potent proinf lammatory cytokine that has pathophysiological roles in several inflammator y conditions. IL-18 mRNA is expressed in a wide range of cells including Ku pffer cells, macrophages, T cells, B cells, dendritic cells, osteoblasts, k eratinocytes, astrocytes, and microglias. Thus, the pathophysiological role of IL-18 has been extensively tested in the organs that contain these cell s. Somewhat surprisingly, IL-18 alone can stimulate Th2 cytokine production as well as allergic inflammation. Therefore, the functions of IL-18 in viv o are very heterogeneous and complicated. In principle, IL-18 enhances the IL-12-driven Th1 immune responses, but it can also stimulate Th2 immune res ponses in the absence of IL-12.