Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats

Sato, M.N.; Yamashiro-Kanashiro, E.H.; Tanji, M.M.; Kaneno, R.; Iqueoka, R.Y.; Duarte, A.J.S.

doi:10.1590/S0036-46651991000300004

Abstracts

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.

Trypanosoma cruzi; Rat; Inbred strain; Cimetidine; Immunoregulation

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} 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

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.

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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.

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.
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.
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.
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.
5. GIFFORD, R.M.; FERGUSON, R.M. & VOSS, B.V. - Cimetidine reduction of tumour formation in mice. Lancet, 1: 638-639, 1981.
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.
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.
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.
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).
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.
11. PALACIOS, R. & ALARCON-SEGOVIA, D. - Cimetidine abrogates suppressor T-cell function in vitro. Immunol. Lett., 3: 33-37, 1981.
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.
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.
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.
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.
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.
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.
18. THOMAS, Y.; HUCHET, R. & GRANJON, D. - Histamine induced suppressor cell of lymphocyte mitogenic response. Cell. Immunol., 59: 268-275, 1981.

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

Publication Dates

Publication in this collection
12 Sept 2006
Date of issue
June 1991

History

Accepted
16 Apr 1991
Received
19 Oct 1990

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 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.

[2] 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.

[3] 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.

[4] 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.

[5] 5. GIFFORD, R.M.; FERGUSON, R.M. & VOSS, B.V. - Cimetidine reduction of tumour formation in mice. Lancet, 1: 638-639, 1981.

[6] 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.

[7] 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.

[8] 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.

[9] 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).

[10] 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.

[11] 11. PALACIOS, R. & ALARCON-SEGOVIA, D. - Cimetidine abrogates suppressor T-cell function in vitro. Immunol. Lett., 3: 33-37, 1981.

[12] 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.

[13] 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.

[14] 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.

[15] 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.

[16] 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.

[17] 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.

[18] 18. THOMAS, Y.; HUCHET, R. & GRANJON, D. - Histamine induced suppressor cell of lymphocyte mitogenic response. Cell. Immunol., 59: 268-275, 1981.

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