| First Author | Fantuzzi G | Year | 1998 |
| Journal | Blood | Volume | 91 |
| Issue | 6 | Pages | 2118-25 |
| PubMed ID | 9490698 | Mgi Jnum | J:46737 |
| Mgi Id | MGI:1202015 | Doi | 10.1182/blood.v91.6.2118.2118_2118_2125 |
| Citation | Fantuzzi G, et al. (1998) Interleukin-18 regulation of interferon gamma production and cell proliferation as shown in interleukin-1beta-converting enzyme (caspase-1)-deficient mice. Blood 91(6):2118-25 |
| abstractText | Interleukin-18 (IL-18) is a costimulatory factor for interferongamma (IFNgamma) production. Processing of pro-IL-18 by IL-1beta-converting enzyme (ICE) leads to the release of bioactive IL-18. Compared with wild-type (WT) mice, splenocytes from ICE-deficient mice produced low IFNgamma after lipopolysaccharide (LPS) or zymosan (50% and 80% reduction). In contrast, IFNgamma production was unimpaired in ICE-deficient mice using Concanavalin A (Con A). Comparable results were obtained when endogenous IL-18 was blocked with a neutralizing antibody. LPS-induced IFNgamma was also reduced by an ICE inhibitor. Exogenous IL-18 augmented zymosan-induced IFNgamma production in WT mice. In ICE-deficient cells, IFNgamma production was only partially restored by IL-18. The reduced levels of IFNgamma in ICE-deficient mice were not due to a lack of IL-12, because zymosan induced IL-12 equally in WT and in ICE-deficient mice. IFNgamma is an important regulator of cell proliferation. In accordance, splenocytes from ICE-deficient mice proliferated more when stimulated with LPS, but not with Con A. Furthermore, in ovalbumin-sensitized ICE-deficient mice, proliferation of lymph node cells in response to the specific antigen was not altered. Exogenous IFNgamma inhibited, whereas blockade of endogenous IFNgamma or IL-18 increased, LPS induced splenocyte proliferation both in WT and in ICE-deficient mice. Our results show that IL-18 is an IL- 12-independent regulator of IFNgamma production and of cell proliferation induced by microbial stimuli. However, ICE-dependent processing of IL-18 is not needed for response to mitogens or antigens. |
