The effect of renin-angiotensin system inhibitors on pro- and anti-inflammatory cytokine production.
The balance between pro- and anti-inflammatory cytokines has been implicated in the pathogenesis of infectious and auto-immune diseases, and its modulation has been proposed as a potential therapeutic target. The results reported in the present study show that modulators of the renin-angiotensin system, such as the angiotensin-converting enzyme (ACE)-inhibitor captopril and the angiotensin II receptor type I antagonist valsartan, have potent inhibitory effects on the lipopolysaccharide (LPS)-stimulated production of pro-inflammatory cytokines tumour necrosis factor (TNF) and interleukin-1 (IL-1) in vitro. The anti-inflammatory cytokine IL-1Ra is increased by captopril, whereas IL-6 production is decreased by valsartan. These effects are exerted mainly at high concentrations of the drugs. Administration of one dose of captopril or valsartan in therapeutic dosages to patients with essential hypertension did not influence LPS-stimulated production of cytokines by whole blood. In conclusion, despite inhibitory effects on pro-inflammatory cytokine production in vitro, it is unlikely that captopril or valsartan could be used in anticytokine therapeutic strategies in vivo.
Department of Medicine, University Hospital Nijmegen, The Netherlands.
A C
AC
Peeters
M G
MG
Netea
B J
BJ
Kullberg
T
T
Thien
J W
JW
van der Meer
D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000276:immunology*; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D013777:Tetrazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D000068756:Valsartan; D002216:Captopril; D014633:Valine