The ACE inhibitors enalapril and captopril modulate cytokine responses in Balb/c and C57Bl/6 normal mice and increase CD4(+)CD103(+)CD25(negative) splenic T cell numbers.
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.
Albuquerque
Deijanira
D
Department of Basic Health Science, Faculty of Medicine, Federal University of Mato Grosso, 78060-900 Cuiabá, Mato Grosso, Brazil. albuquerqued@yahoo.com
Nihei
Jorge
J
Cardillo
Fabíola
F
Singh
Ram
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004656:Enalapril / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D039001:Integrin alpha Chains / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D015703:Antigens, CD; D015704:CD4 Antigens; D016207:Cytokines; D039001:Integrin alpha Chains; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; C091367:alpha E integrins; D016753:Interleukin-10; D004656:Enalapril; D002216:Captopril