A ROLE FOR T-HELPER TYPE-1 AND TYPE-2 CYTOKINES IN THE REGULATION OF HUMAN MONOCYTE APOPTOSIS

T-helper type-1 (Th1) and type-2 (Th2) cytokines, respectively, favor T-cell-mediated immunity and defense against intracellular pathogens o r antibody-mediated immunity and defense against extracellular pathoge ns, Here we report that type-1 and type-2 cytokines also exert a regul atory effect on human monocyte survival. Interleukin-12 (IL-12) enhanc ed survival in long-term (10 days) cultures of adherent monocytes, whe reas IL-10 induced death by apoptosis, In short-term cultures (2 days) , the Th2 cytokines, IL-10 and IL-4, enhanced apoptosis; however, the Th1 cytokines, IL-12 and IL-2 only showed a reducing effect an monocyt e apoptosis in culture conditions that decreased monocyte adhesion lea ding to increased levels of spontaneous apoptosis; finally, the Th 1 c ytokine, interferon-gamma (IFN-gamma), acted in a dose-dependent fashi on: At high concentrations, IFN-gamma enhanced apoptosis, which is an effect related to IL-10 secretion and reduced by antibodies to IL-10. Th1 cytokines reduced monocyte apoptosis induced by several stimuli: I L-2 reduced apoptosis induced by either IL-10 or high concentrations o f IFN-gamma, IL-12 reduced apoptosis induced by either the ligation of the Fas (CD95) molecule or gamma-irradiation, and IFN-gamma (at low d oses that did not trigger apoptosis) reduced apoptosis induced by gamm a-irradiation. These findings suggest that the regulatory role of type -1 and type-a cytokines on the development of immune responses and inf lammatory reactions also involves the regulation of monocyte death by apoptosis. (C) 1997 by The American Society of Hematology.