CAPTOPRIL AND LISINOPRIL SUPPRESS PRODUCTION OF INTERLEUKIN-12 BY HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Angiotensin converting enzyme (ACE) inhibitors have immunomodulatory f unctions and can suppress a number of proinflammatory, monocyte/macrop hage-derived cytokines. Interleukin-12 is a cytokine produced primaril y by monocytes and macrophages, which plays an essential role in cell mediated immunity and stimulates the development of T helper type 1 im mune responses. In this study, we investigated the ability of ACE inhi bitors, captopril and lisinopril, to suppress IL-12 production by huma n peripheral blood mononuclear cells (PBMC). We show that both ACE inh ibitors significantly inhibit production of IL-12 by PBMC stimulated w ith bacterial lipopolysaccharide (LPS) or Staphylococcus aureus Cowan (SAC). Although both ACE inhibitors also suppressed IFN-gamma producti on by human anti-CD3/anti-CD28-stimulated T-cells, the addition of exo genous IFN-gamma to the PBMC stimulation medium does not abrogate the ability of ACE inhibitors to suppress IL-12 production. Inhibition of IL-12 was not associated with inhibition of IL-1 gamma, but correlated with the suppression of ACE. Therefore, suppression of IL-12 may cont ribute to the immunomodulatory effect of ACE inhibitors and may be res ponsible for the beneficial effect of captopril and other ACE inhibito rs in inflammatory or autoimmune conditions in which IL-12 is involved . (C) 1998 Elsevier Science B.V. All rights reserved.