Efeito imunomodulatório da cimetidina sobre a resposta blastogênica de esplenócitos de ratos infectados por T. cruzi

rimtsp Revista do Instituto de Medicina Tropical de São Paulo Rev. Inst. Med. trop. S. Paulo 1678-9946 Instituto de Medicina Tropical São Paulo, SP, Brazil O efeito imunomodulatório da Cimetidine (CIM), um antagonista do receptor de histamina-tipo 2, foi avaliado na resposta blastogênica a Con A em células de ratos Wistar Furth (WF) infectados pela cepa Y de Trypanosoma cruzi (T. cruzi). Foi observado que apenas na concentração de 10-3M de Cimetidine houve amplificação da resposta blastogênica de esplenócitos normais a Con A. Entretanto, a capacidade mitogênica de esplenócitos de animais infectados foi restaurada na presença de molaridades da droga que variaram entre 10-8 a 10-3. Os resultados demonstraram que a CIM tem o potencial de modular a resposta mitogênica de células de animais infectados pelo T. cruzi, sugerindo um papel imunoregulatório da histamina e/ou células que expressam receptores H2 nesta infecção. ORIGINAL ARTICLES Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats Efeito imunomodulatório da cimetidina sobre a resposta blastogênica de esplenócitos de ratos infectados por T. cruzi M.N. Sato; E.H. Yamashiro-Kanashiro; M.M. Tanji; R. Kaneno; R.Y. Iqueoka; A.J.S. Duarte Laboratório de Imunogenética e Transplante Experimental (LIM 73) da Disciplina de Alergia e Imunopatologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP Address for correspondence SUMMARY The immunomodulatory effect of cimetidine (CIM), a histamine type-2 receptor antagonist, was evaluated in respect to the blastogenic response to Con A of Wistar Furth (WF) rats infected by the Y strain of Trypanosoma cruzi (T. cruzi). Enhancement of blastogenesis of normal splenocytes was observed at a concentration of 10-3M. However, the splenocytes from infected animals responded to concentrations of CIM ranging from 10-8 to 10-3M. The mitogenic response to Con A of cells from infected animals was restored in the presence of CIM. The results show that CIM modulates the "in vitro" proliferative response of cells from T. cruzi-infected rats and suggest an immunoregulatory role of histamine and/or of cells that express H2 receptors in this infection. Key words: Trypanosoma cruzi; Rat; Inbred strain; Cimetidine; Immunoregulation. RESUMO O efeito imunomodulatório da Cimetidine (CIM), um antagonista do receptor de histamina-tipo 2, foi avaliado na resposta blastogênica a Con A em células de ratos Wistar Furth (WF) infectados pela cepa Y de Trypanosoma cruzi (T. cruzi). Foi observado que apenas na concentração de 10-3M de Cimetidine houve amplificação da resposta blastogênica de esplenócitos normais a Con A. Entretanto, a capacidade mitogênica de esplenócitos de animais infectados foi restaurada na presença de molaridades da droga que variaram entre 10-8 a 10-3. Os resultados demonstraram que a CIM tem o potencial de modular a resposta mitogênica de células de animais infectados pelo T. cruzi, sugerindo um papel imunoregulatório da histamina e/ou células que expressam receptores H2 nesta infecção. Full text available only in PDF format. Texto completo disponible sólo en PDF. ACKNOWLEDGEMENTS We wish thank Dr. Judith Kloetzel for providing Y strain of T. cruzi, Maria Celia Rezende for maintenance of inbred rats. Edna de Souza Joaquim for providing us with reagents, Maria de Lourdes Moura Antonio for secretarial work, Luiz Augusto Marcondes Fonseca and Dewton Vasconcelos for reviewing this manuscript. Research supported by FINEP (PADCT, nº 43.84.0819.00), CNPq (nº 403749/82) and LIM/HC/FMUSP. Address for correspondence: Dr. Alberto J.S. Duarte Faculdade de Medicina da Universidade de São Paulo, Laboratório de Imunogenética e Transplante Experimental (LIM-73) Av. Dr. Arnaldo, 455 - 2º andar - sala 105A CEP 01246 São Paulo, SP. Brazil Recebido para publicação em 19/10/1990 Aceito para publicação em 16/4/1991 1. BADGER, A.M.; YOUNG, J. & POSTE, G. - Inhibition of phytohemagglutinin-induced proliferation of human peripheral blood lymphocytes by histamine H1 and H2 agonists. Clin. exp. Immunol., 51: 178-184, 1983. Inhibition of phytohemagglutinin-induced proliferation of human peripheral blood lymphocytes by histamine H1 and H2 agonists Clin. exp. Immunol. 1983 178 184 51 BADGER A.M. YOUNG J. POSTE G. 2. BARSOUM, I.S.; DAHAWI, H.S.S.; GAMIL, F.M.; EL ALAMY, M.A. & COLLEY, D.G. - Immune responses and immunoregulation in relation to human schistosomiasis in Egypt II. Cimetidine reversal of histamine-mediated suppression of antigen-induced blastogenesis. J. Immunol., 133: 1576-1580, 1984. Immune responses and immunoregulation in relation to human schistosomiasis in Egypt II: Cimetidine reversal of histamine-mediated suppression of antigen-induced blastogenesis J. Immunol. 1984 1576 1580 133 BARSOUM I.S. DAHAWI H.S.S. GAMIL F.M. EL ALAMY M.A. COLLEY D.G. 3. BEER, D.J.; ROSENWASSER, L.J.; DINARELLO, C.A. & ROCKLIN, R.E. - Cellular interaction in the generation and expression of histamine-induced suppressor activity, Cell. Immunol., 69: 101-112, 1982. Cellular interaction in the generation and expression of histamine-induced suppressor activity, Cell Immunol. 1982 101 112 69 BEER D.J. ROSENWASSER L.J. DINARELLO C.A. ROCKLIN R.E. 4. GIFFORD, R.M.; HATFIELD, S.M. & SCHMIDTKE, J.R. - Cimetidine - induced augmentation of human lymphocyte blastogenesis by mitogen, bacterial antigen, and alloantigen. Transplantation, 29: 143-148, 1980. Cimetidine: induced augmentation of human lymphocyte blastogenesis by mitogen, bacterial antigen, and alloantigen Transplantation 1980 143 148 29 GIFFORD R.M. HATFIELD S.M. SCHMIDTKE J.R. 5. GIFFORD, R.M.; FERGUSON, R.M. & VOSS, B.V. - Cimetidine reduction of tumour formation in mice. Lancet, 1: 638-639, 1981. Cimetidine reduction of tumour formation in mice Lancet 1981 638 639 1 GIFFORD R.M. FERGUSON R.M. VOSS B.V. 6. KIERSZENBAUM, F. - Immunologic deficiency during experimental Chagas disease (Trypanosoma cruzi infection): role of adherent, nonspecific esterase-positive spleen cells. J. Immunol., 129, 2202-2205, 1982. Immunologic deficiency during experimental Chagas disease (Trypanosoma cruzi infection): role of adherent, nonspecific esterase-positive spleen cells J. Immunol. 1982 2202 2205 129 KIERSZENBAUM F. 7. LIEW, F.Y.; SCHMIDT, J.A.; DONG, L.S.; MILLOT, S.M.; DHALIWAL, J.S. & CROFT, S.L. - Suppressive substance produced by T cell from mice chronically infected with Trypanosoma cruzi. J. Immunol., 140: 969-973, 1988. Suppressive substance produced by T cell from mice chronically infected with Trypanosoma cruzi J. Immunol. 1988 969 973 140 LIEW F.Y. SCHMIDT J.A. DONG L.S. MILLOT S.M. DHALIWAL J.S. CROFT S.L. 8. LIMA, M. & ROCKLIN, R.E. - Histamine modulates in vitro IgG production by pokeweed mitogen-stimulated human mononuclear cells. Cell. Immunol., 64: 324-336, 1981. Histamine modulates in vitro IgG production by pokeweed mitogen-stimulated human mononuclear cells Cell. Immunol. 1981 324 336 64 LIMA M. ROCKLIN R.E. 9. SATO, M.N.; TANJI, M.M.; YAMASHIRO-KANASHIRO, E.H.; BONADIA, M.R.M. & DUARTE, A.J.S. - Mononuclear cells subpopulations in spleen and blood of inbred rats during the acute phase of infection by Y strain of T. cruzi. In: ANNUAL MEETING ON BASIC RESEARCH IN CHAGAS DISEASE, 23., Caxambú, 1986. p.145. (Mem. Inst. Oswaldo Cruz, 81: 145, 1986). Mononuclear cells subpopulations in spleen and blood of inbred rats during the acute phase of infection by Y strain of T. cruzi Mem. Inst. Oswaldo Cruz 1986 145 81 SATO M.N. TANJI M.M. YAMASHIRO-KANASHIRO E.H. BONADIA M.R.M. DUARTE A.J.S. 10. NAIR, M.N.P. & SCHWARTZ, S.A. - Effect of histamine and histamine antagonist on natural and antibody-dependent cellular cytotoxicity of human lymphocytes in vitro. Cell. Immunol., 81: 45-60, 1983. Effect of histamine and histamine antagonist on natural and antibody-dependent cellular cytotoxicity of human lymphocytes in vitro Cell. Immunol. 1983 45 60 81 NAIR M.N.P. SCHWARTZ S.A. 11. PALACIOS, R. & ALARCON-SEGOVIA, D. - Cimetidine abrogates suppressor T-cell function in vitro. Immunol. Lett., 3: 33-37, 1981. Cimetidine abrogates suppressor T-cell function in vitro Immunol. Lett. 1981 33 37 3 PALACIOS R. ALARCON-SEGOVIA D. 12. RAMOS, C.; SCHADTLER-SIWON, I. & ORTIZ-ORTIZ, L.- Suppressor cells present in the spleens of Trypanosoma cruzi-infected mice. J. Immunol., 122: 1243-1247, 1979. Suppressor cells present in the spleens of Trypanosoma cruzi-infected mice J. Immunol. 1979 1243 1247 122 RAMOS C. SCHADTLER-SIWON I. ORTIZ-ORTIZ L. 13. ROCKLIN, R.E. - Modulation of cellular immune responses in vivo and in vitro by histamine receptor-bearing lymphocytes. J. clin. Invest., 57: 1051-1058, 1976. Modulation of cellular immune responses in vivo and in vitro by histamine receptor-bearing lymphocytes J. clin. Invest. 1976 1051 1058 57 ROCKLIN R.E. 14. ROCKLIN, R.E.; BREARD, J.; GUPTA, S.; GOOD, R.A. & MELMON, K.L. - Characterization of the human blood lymphocytes that produce a histamine-induced suppressor factor. Cell. Immunol., 51: 226-237, 1980. Characterization of the human blood lymphocytes that produce a histamine-induced suppressor factor Cell. Immunol. 1980 226 237 51 ROCKLIN R.E. BREARD J. GUPTA S. GOOD R.A. MELMON K.L. 15. RUFF, A.J.; LEIVA, L.E; LAMMIE, P.J. & KATZ, S.P. - Failure of the H2 antagonist cimetidine to reverse parasite antigen-specific lymphocyte unresponsiveness in experimental filariasis. Clin. exp. Immunol., 74: 26-31, 1988. Failure of the H2 antagonist cimetidine to reverse parasite antigen-specific lymphocyte unresponsiveness in experimental filariasis Clin. exp. Immunol. 1988 26 31 74 RUFF A.J. LEIVA L.E LAMMIE P.J. KATZ S.P. 16. SCHWARTZ, A.; ASKENASE, P.W. & GERSHON, R.K. - Histamine inhibition of the in vitro induction of cytotoxic T cells. Immunopharmacology, 2: 179-190, 1980. Histamine inhibition of the in vitro induction of cytotoxic T cells Immunopharmacology 1980 179 190 2 SCHWARTZ A. ASKENASE P.W. GERSHON R.K. 17. TARLETON, R.L. - Trypanosoma cruzi-induced suppression of IL-2 production. II. Evidence for a role suppressor cells. J. Immunol., 140: 2769-2773, 1988. Trypanosoma cruzi-induced suppression of IL-2 production.: II. Evidence for a role suppressor cells J. Immunol. 1988 2769 2773 140 TARLETON R.L. 18. THOMAS, Y.; HUCHET, R. & GRANJON, D. - Histamine induced suppressor cell of lymphocyte mitogenic response. Cell. Immunol., 59: 268-275, 1981. Histamine induced suppressor cell of lymphocyte mitogenic response Cell. Immunol. 1981 268 275 59 THOMAS Y. HUCHET R. GRANJON D.