IFN-beta inhibits the ability of T lymphocytes to induce TNF-alpha and IL-1 beta production in monocytes upon direct cell-cell contact

Tumour necrosis factor (TNF)-alpha and interleukin (IL-)1 beta, essential p layers in the pathogenesis of immune-inflammatory diseases, are strongly in duced in monocytes by direct contact with stimulated T lymphocytes. The pre sent study shows that the latter mechanism is inhibited by interferon (IFN) -beta. In co-cultures of autologous T lymphocytes and monocytes stimulated by phytohaemagglutinin (PHA), IFN-beta inhibited the production of TNF-alph a and IL-1 beta by 88 and 98%, respectively, whereas the simultaneous produ ction of IL-1 receptor antagonist (IL-1Ra), was enhanced two-fold. The latt er effects of IFN-beta were independent of modulations in IFN-gamma, IL-4 a nd IL-10 production. When monocytes were activated by plasma membranes of s timulated T cells, IFN-beta slightly inhibited the production of TNF-alpha and IL-1 beta, while enhancing 1.5-fold that of IL-1Ra, The latter effect c orrelated with the persistence of high steady-state levels of IL-1Ra mRNA a fter 24 h of activation. Membranes isolated from T lymphocytes that had bee n stimulated in the presence of IFN-beta displayed a 80% decrease in their capacity to induce the production of IL-1 beta and TNF-alpha in monocytes, whereas IL-1Ra induction was decreased by only 32%, These results demonstra te that IFN-beta modulates contact-mediated activation of monocytes by acti ng on both T lymphocytes and monocytes, decreasing the ability of T lymphoc ytes to induce TNF-alpha and IL-1 beta production in monocytes and directly enhancing the production of IL-1Ra in the latter cells. (C) 2001 Academic Press.