title: Angiotensin-converting-enzyme inhibitors suppress synthesis of tumour necrosis factor and interleukin 1 by human peripheral blood mononuclear cells.
abstract: Administration of angiotensin-converting-enzyme (ACE) inhibitors reduce vascular proliferation following endothelial injury as well as progression of renal disease in various animal models. These effects might be due to interference with cytokines such as interleukin 1 (IL-1) or tumour necrosis factor alpha (TNF) since they have been implicated in regulating the effects of vascular cell growth factors such as fibroblast- and platelet-derived growth factors. We investigated the in vitro synthesis of IL-1 and TNF from human peripheral blood mononuclear cells (PBMC) in the presence of various ACE-inhibitors. Captopril dose-dependently suppressed the IL-1 beta-induced synthesis of TNF by 74% (P < 0.01) and the IL-1 beta-induced synthesis of IL-1 alpha by 60% (P < 0.01). Cytokine synthesis induced by lipopolysaccharide was less affected. At concentrations suppressing TNF and IL-1, captopril did not reduce the synthesis of complement C3 in the same cells. Enalapril and cilazapril also suppressed cytokine-induced cytokine synthesis. Ramipril, lisinopril, perindopril and spirapril had no significant effect on TNF synthesis suggesting that the effect was not related specifically to the inhibition of ACE. Accumulation of mRNA for IL-1 and TNF were not affected by captopril, suggesting a posttranscriptional effect. We conclude that certain ACE-inhibitors suppress IL-1 and TNF synthesis at a posttranscriptional level and might therefore influence cytokine-mediated cell growth.
authors.affiliation: Department of Nephrology, Medical School Hannover, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schindler
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: K M
authors.initials: KM
authors.lastname: Koch
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D003864:Depression, Chemical; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D002216:Captopril