Abstract
We observed histopathological and ultrastructural hepatic changes following the intracardiac inoculation ofLeishmania donovani amastigotes into inbred LHC hamsters (group I). Since granuloma formation is known to be T-cell-dependent, we also examined infected hamsters under cyclophosphamide immunosuppressive treatment (group ICy) and evaluated the production of interleukin-2 (IL-2) by their cells. Group I showed more intense hepatocyte and endothelial cell clasmatosis as well as hepatocyte degeneration and necrosis, deposits of connective tissue fibers, granulomas with multinucleated giant cells (MGCs) of foreign-body and Langhans' types and reduced production of IL-2 by spleen cells. In contrast, group ICy hamsters exhibited larger eosinophil and lymphocyte populations within sinusoids and peri-sinusoidal areas but showed no MGCs in granulomas. A striking decline in IL-2 production was noted. These results suggest that cyclophosphamide induces a delay in the natural evolution ofL. donovani-induced granulomatous hepatic inflammation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adams DO (1976) The granulomatous inflammatory resonse. Am J Pathol 84:164–191
Barbosa AA Jr, Andrade ZA, Reed SG (1987) The pathology of experimental visceral leishmaniasis in resistant and susceptible lines of inbred mice. Braz J Med Biol Res 20:63–72
Bunn-Moreno MM, Madeira ED, Miller K, Menezes JA, Campos-Neto A (1985) Hypergammaglobulinaemia inLeishmania donovani-infected hamsters: possible association with a polyclonal activator of B cells and with suppression of T cell function. Clin Exp Immunol 59:427–434
Cavalho EM, Badaró R, Reed SC, Jones TC, Johnson WD (1985a) Absence of gamma interferon and interleukin-2 production during active visceral leishmaniasis. J Clin Invest 76:2066–2069
Carvalho EM, D'Oliveira A Jr, Queiroz AC (1985b) Immunopatologia do baco na leishmaniose visceral. Rev Bras Med Trop 18:109–112
Duarte MIS, Corbett CEP (1987 Histopathological patterns of the liver involvement in visceral leishmaniasis. Rev Inst Med Trop São Paulo 29:131–136
Gifawesen C, Farrel JP (1989) Comparison of T-cell responses in self-limiting versus progressive visceralLeishmania donovani infections in golden hamsters. Infect Immun 57:3091–3096
Gutierrez Y, Maksen JA, Reiner NE (1984) Pathologic changes in murine leishmaniasis (Leishmania donovani) with special reference to the dynamics of granuloma formation in the liver. Am J Pathol 114:222–230
Kreipe H, Radzun HJ, Rudolph P, Barth J, Hansmann ML, Heidorn K, Parwaresch MR (1988) Multinucleared giant cells generated in vitro: terminally differentiated macrophages with down-regulated c-fms expression. Am J Pathol 130:232–243
Lammas DA, Mitchell A, Wakelin D (1988) Genetic control of eosinophilial in parasitic infections: responses of mouse strains to treatment with cyclophosphamide and parasite antigen. Int J Parasitol 18:1077–1085
McElrath MJ, Murray HW, Cohn ZA (1988) The dynamics of granuloma formation in experimental visceral leishmaniasis. J Exp Med 167:1927–1937
McInnes A, Rennick DM (1988) Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells. J Exp Med 167:598–611
Meleney HE (1925) The histopathology of kala-azain the hamster, monkey and man. Am J Pathol 1:147–168
Murray HW, Stern JJ, Welte K, Rubin BY, Carriero SM, Nathan CF (1987) Experimental visceral leishmaniasis: production of interleukin-2 and interferon-γ, tissue immune reaction, and response to treatment with interleukin-2 and interferon-γ. J Immunol 138:2290–2297
Oliveira A, Roque-Barreira MC, Sartori A, Campos-Neto A, Rossi MA (1985) Mesangial proliferative glomerunephritis associated with progressive amyloid deposition in hamster experimentally infected withLeishmania donovani. Am J Pathol 120:256–262
Reiner NE, Finke JH (1983) Interleukin-2 deficiency in murine leishmaniasis donovani and its relationships to depressed spleen cell responses to phytohemagglutinin. J Immunol 131:1487–1491
Schlesinger L, Musson RA, Johnson RB (1984) Functional and biochemical studies of multinucleated giant cells derived from the culture of human monocytes. J Exp Med 159:1289–1294
Sen Gupta PC, Chakravarty NK, Ray HN, Das Gupta B (1956) The liver in kala-azar. Ann Trop Med Parasitol 50:252–259
Thomson AW, Mathie IH, Sewell HF (1987) Cyclophosphamide-induced eosinophilia in the rat: concomitant changes in T-cell subsets. B cells and large granular lymphocytes within lymphoid tissues. Immunology 60:383–388
Timerman A, Hutzler RU, Veronesi R (1986) Fibrose hepática no calazar. Rev Bras Med 43:135–139
Veres B, Omer A, Satir A, Al Hassan A (1977) Morphology of the spleen and lymph nodes in fatal visceral leishmaniasis. Immunology 33:605–610
Wilson ME, Innes DJ, Souza AQ, Pearson RD (1987) Early Instopathology of experimental infection withLeishmanio donomani in hamsters. J Parasitol 73:55–63
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Baldo Corrêa, E., Cunha, J.M.T., Bunn-Moreno, M.M. et al. Cyclophosphamide affects the dynamics of granuloma formation in experimental visceral leishmaniasis. Parasitol Res 78, 154–160 (1992). https://doi.org/10.1007/BF00931658
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00931658