The inhibitory effect of tumor necrosis factor and interleukin-1 on Ia induction by interferon-gamma on endothelial cells from murine central nervous system microvessels.

The effect of both tumor necrosis factor-alpha (TNF) and interleukin-1 (IL-1) on interferon-gamma (IFN)-induced Ia expression was studied using cultured endothelial cells (EC) isolated from cerebral microvessels of SJL mice. TNF inhibited Ia induction by IFN in a dose-dependent manner. The degree of inhibition by TNF was related to the IFN concentration: 200 U/ml TNF inhibited Ia expression induced by 20 U/ml IFN by 80% and Ia induced by 100 U/ml IFN by 45%. FACS analysis revealed the induction of Ia antigen on 30-40% of EC after 3 days' culture with IFN; TNF significantly reduced the percent of EC expressing Ia antigens. Identical treatment of SJL astrocytes showed TNF augmented Ia expression induced by IFN. IL-1 also inhibited Ia induction by IFN in a manner similar to that observed with TNF. The percent reduction of Ia-positive EC by Il-1 (2.0 U/ml) was 30% and 50% during incubations with 100 and 20 U/ml IFN, respectively. When combined at suboptimal concentrations IL-1 and TNF synergistically inhibited Ia expression induced by IFN. These results demonstrate that TNF acts on EC and astrocytes in a disparate manner and indicate that TNF and IL-1 can synergistically down-regulate immune responses involving central nervous system EC.