title: IFN-beta inhibits the ability of T lymphocytes to induce TNF-alpha and IL-1beta production in monocytes upon direct cell-cell contact.
abstract: Tumour necrosis factor (TNF)-alpha and interleukin (IL-)1beta, essential players in the pathogenesis of immuno-inflammatory diseases, are strongly induced in monocytes by direct contact with stimulated T lymphocytes. The present 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-alpha and IL-1beta by 88 and 98%, respectively, whereas the simultaneous production of IL-1 receptor antagonist (IL-1Ra), was enhanced two-fold. The latter effects of IFN-beta were independent of modulations in IFN-gamma, IL-4 and IL-10 production. When monocytes were activated by plasma membranes of stimulated T cells, IFN-beta slightly inhibited the production of TNF-alpha and IL-1beta, while enhancing 1.5-fold that of IL-1Ra. The latter effect correlated with the persistence of high steady-state levels of IL-1Ra mRNA after 24 h of activation. Membranes isolated from T lymphocytes that had been stimulated in the presence of IFN-beta displayed a 80% decrease in their capacity to induce the production of IL-1beta and TNF-alpha in monocytes, whereas IL-1Ra induction was decreased by only 32%. These results demonstrate that IFN-beta modulates contact-mediated activation of monocytes by acting on both T lymphocytes and monocytes, decreasing the ability of T lymphocytes to induce TNF-alpha and IL-1beta production in monocytes and directly enhancing the production of IL-1Ra in the latter cells.
authors.affiliation: Division of Immunology and Allergy, Clinical Immunology Unit (Hans Wilsdorf Laboratory), Department of Internal Medicine, University Hospital, Geneva, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Jungo
authors.forename: J M
authors.initials: JM
authors.lastname: Dayer
authors.forename: C
authors.initials: C
authors.lastname: Modoux
authors.forename: N
authors.initials: N
authors.lastname: Hyka
authors.forename: D
authors.initials: D
authors.lastname: Burger
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism; D018448:Models, Immunological; D009000:Monocytes / Q000276:immunology*; D020871:RNA Stability; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008565:Membrane Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D016899:Interferon-beta; D007371:Interferon-gamma