The ACE inhibitors enalapril and captopril modulate cytokine responses in Balb/c and C57Bl/6 normal mice and increase CD4+CD103+CD25negative splenic T cell numbers

Abstract

Increasing evidence implies beneficial effects of angiotensin-converting enzyme (ACE) inhibitors beyond those of their original indications to control hypertension. One of the most attractive non-hemodynamic properties of ACE inhibitors is their ability to regulate cytokine production. The mechanism(s) underlying the role of ACE inhibitors on cytokine synthesis are not well understood but they have traditionally been attributed to the inhibition of angiotensin (Ang) II formation. In fact, it has been extensively demonstrated that ACE inhibitors decrease Ang II-induced production of proinflammatory cytokines and chemokines. However, it is not well described if inhibition of endogenous Ang II generation by ACE inhibitors modulates systemic cytokine production in mice. To verify that, in this work, we investigated the effects of treatment with the ACE inhibitors enalapril and captopril on cytokine synthesis in C57Bl/6 and Balb/c mice. Our results show that enalapril up regulates IL-10 produced by splenocytes from Balb/c and C57Bl/6 mice and captopril increased it only in Balb/c mice. Furthermore, CD4(+)CD103(+) presented increased IL-10 production after enalapril treatment. Enalapril as well as captopril short-term treatment enhanced IL-2 synthesis in Balb/c mice. Besides, enhanced IL-2 and IL-10 levels correlates with increased CD4(+)CD103(+)CD25(negative) T cells numbers in spleens from enalapril-treated mice.

Captopril protects against burn-induced cardiopulmonary injury in rats

“…Captopril has been shown to express immune-regulating, antioxidant and anti-inflammatory properties. [34] In agreement with these studies, our results showed that depressing cytokine expression is associated with improved cardiac function.…”

Enalapril treatment increases T cell number and promotes polarization towards M1-like macrophages locally in diabetic nephropathy

“…ACE inhibition is clinically associated with reduction of urinary MCP-1 levels and in pre-clinical models of remnant kidney disease it has been shown to prevent local proliferation of macrophages and myofibroblasts in the kidney [57]. However, Albuquerque et al showed that enalapril treatment potently increases the number of CD4 + T cells in the spleen together with the increasing production of IL-2 and IL-10 [58]. Our observation that the overall kidney associated leukocyte number, specifically the CD4 + /CD8 + T cells, is increased after enalapril treatment in both db/db and STZ treated mice demonstrates that the angiotensin II blockade overall seems to favor proliferation or attraction of lymphocytes specifically in advanced disease.…”

Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonist attenuate tumor growth via polarization of neutrophils toward an antitumor phenotype

“…Tumor-bearing mice were administered captopril in their drinking water at 1, 10, 50, or 100 mg/kg/d; these are typical, murine therapeutic dosages. 23,24 Captopril attenuated tumor growth in a dose-dependent fashion ( Fig. 2A).…”