The effect of renin–angiotensin system inhibitors on pro‐ and anti‐inflammatory cytokine production

Peeters, A. C. T. M.; Netea, Mihai G.; Kullberg, Bart Jan; Thien, Th.; Meer, J.W.M. van der

doi:10.1046/j.1365-2567.1998.00524.x

Cited by 93 publications

(73 citation statements)

References 24 publications

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“…5). Our results are in accordance with those showing that proinflammatory and anti-inflammatory cytokines secreted by human PBMCs are not affected by captopril administration (52). These results are also counter to those of other groups reporting that captopril enhances T cell function in their model systems (53)(54)(55)(56).…”

Section: Discussionsupporting

confidence: 91%

Captopril Prevents Experimental Autoimmune Myocarditis

Godsel

León

Wang

et al. 2003

The Journal of Immunology

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Captopril, an angiotensin-converting enzyme inhibitor, is widely used in the treatment of a variety of cardiomyopathies, but its effect on autoimmune myocarditis has not been addressed experimentally. We investigated the effect of captopril on myosin-induced experimental autoimmune myocarditis. A/J mice, immunized with syngeneic cardiac myosin, were given 75 mg/L of captopril in their drinking water. Captopril dramatically reduced the incidence and severity of myocarditis, which was accompanied by a reduction in heart weight to body weight ratio and heart weight. Captopril specifically interfered with cell-mediated immunity as myosin delayed-type hypersensitivity (DTH) was reduced, while anti-myosin Ab production was not affected. Captopril-treated, OVA-immunized mice also exhibited a decrease in OVA DTH. In myosin-immunized, untreated mice, injection of captopril directly into the test site also suppressed myosin DTH. Interestingly, captopril did not directly affect Ag-specific T cell responsiveness because neither in vivo nor in vitro captopril treatment affected the proliferation, IFN-γ secretion, or IL-2 secretion by Ag-stimulated cultured splenocytes. These results indicate that captopril ameliorates experimental autoimmune myocarditis and may act, at least in part, by interfering with the recruitment of cells to sites of inflammation and the local inflammatory environment.

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Section: Discussionsupporting

confidence: 91%

Captopril Prevents Experimental Autoimmune Myocarditis

Godsel

León

Wang

et al. 2003

The Journal of Immunology

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“…There is also evidence to suggest that formation of Ang II may contribute to the loss of body tissue in mice bearing the MAC16 tumour, since imidapril attenuated the development of weight loss in this model. Ang II directly stimulates tumour necrosis factor-a (TNF-a) and interleukin-6 (IL-6) production in human peripheral monocytes and ACE inhibitors inhibit LPS-induced TNF-a production (Peeters et al, 1998). However, the activity of imidapril in the MAC16 model could not be explained by an effect on TNF-a or IL-6 production, since we have previously shown no involvement of these cytokines in the cachectic process in this model (Mulligan et al, 1992).…”

Section: Discussionmentioning

confidence: 91%

Angiotensin II directly induces muscle protein catabolism through the ubiquitin–proteasome proteolytic pathway and may play a role in cancer cachexia

2005

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The ability of angiotensin I (Ang I) and II (Ang II) to induce directly protein degradation in skeletal muscle has been studied in murine myotubes. Angiotensin I stimulated protein degradation with a parabolic dose -response curve and with a maximal effect between 0.05 and 0.1 mM. The effect was attenuated by coincubation with the angiotensin-converting enzyme (ACE) inhibitor imidaprilat, suggesting that angiotensin I stimulated protein degradation through conversion to Ang II. Angiotensin II also stimulated protein breakdown with a similar dose -response curve, and with a maximal effect between 1 and 2.5 mM. Total protein degradation, induced by both Ang I and Ang II, was attenuated by the proteasome inhibitors lactacystin (5 mM) and MG132 (10 mM), suggesting that the effect was mediated through upregulation of the ubiquitin -proteasome proteolytic pathway. Both Ang I and Ang II stimulated an increased proteasome 'chymotrypsin-like' enzyme activity as well as an increase in protein expression of 20S proteasome a-subunits, the 19S subunits MSS1 and p42, at the same concentrations as those inducing protein degradation. The effect of Ang I was attenuated by imidaprilat, confirming that it arose from conversion to Ang II. These results suggest that Ang II stimulates protein degradation in myotubes through induction of the ubiquitin -proteasome pathway. Protein degradation induced by Ang II was inhibited by insulin-like growth factor and by the polyunsaturated fatty acid, eicosapentaenoic acid. These results suggest that Ang II has the potential to cause muscle atrophy through an increase in protein degradation. The highly lipophilic ACE inhibitor imidapril (Vitort) (30 mg kg À1 ) attenuated the development of weight loss in mice bearing the MAC16 tumour, suggesting that Ang II may play a role in the development of cachexia in this model.

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“…The benecial effects of ACE inhibitors have mainly been attributed to diminished cardiac workload by interference with the renin -angiotensin-aldosterone system. However, ACE inhibitors have subsequently been shown to possess anti-in ammatory properties (8) and it may be speculated that some of the bene cial effects of ACE inhibitors are conferred by such activities. For example, it was recently shown that reduced cardiac septum thickness after enalapril treatment in congestive heart failure patients was related to decreased inammation (9).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

New insights into the wasting mechanisms of chronic disease

Cederholm¹

2002

Scandinavian Journal of Nutrition

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The effect of renin–angiotensin system inhibitors on pro‐ and anti‐inflammatory cytokine production

Cited by 93 publications

References 24 publications

Captopril Prevents Experimental Autoimmune Myocarditis

Captopril Prevents Experimental Autoimmune Myocarditis

Angiotensin II directly induces muscle protein catabolism through the ubiquitin–proteasome proteolytic pathway and may play a role in cancer cachexia

New insights into the wasting mechanisms of chronic disease

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