THE EFFECT OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS ON PROINFLAMMATORY AND ANTIINFLAMMATORY CYTOKINE PRODUCTION

The balance between pro- and anti-inflammatory cytokines has been impl icated in the pathogenesis of infectious and auto-immune diseases, and its modulation has been proposed as a potential therapeutic target. T he results reported in the present study show that modulators of the r enin-angiotensin system, such as the angiotensin-converting enzyme (AC E)-inhibitor captopril and the angiotensin II receptor type I antagoni st valsartan, have potent inhibitory effects on the lipopolysaccharide (LPS)-stimulated production of pro-inflammatory cytokines tumour necr osis factor (TNF) and interleukin-1 (IL-1) in vitro. The anti-inflamma tory cytokine IL-1Ra is increased by captopril, whereas IL-6 productio n is decreased by valsartan. These effects are exerted mainly at high concentrations of the drugs. Administration of one dose of captopril o r valsartan in therapeutic dosages to patients with essential hyperten sion did not influence LPS-stimulated production of cytokines by whole blood. In conclusion, despite inhibitory effects on proinflammatory c ytokine production in vitro, it is unlikely that captopril or valsarta n could be used in anticytokine therapeutic strategies in vivo.