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Infection and Immunity, December 2002, p. 6734-6740, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6734-6740.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Up-Regulation of Th1-Type Responses in Mucosal Leishmaniasis Patients

Olívia Bacellar,1 Hélio Lessa,1 Albert Schriefer,1 Paulo Machado,1 Amélia Ribeiro de Jesus,1 Walderez O. Dutra,2 Kenneth J. Gollob,2 and Edgar M. Carvalho1*

Serviço de Imunologia do Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia,1 Universidade Federal de Minas Gerais-ICB, Departamento de Bioquímica-Imunologia, Departamento de Morfologia, Belo Horizonte, MG, Brazil2

Received 26 April 2002/ Returned for modification 20 June 2002/ Accepted 24 August 2002

The cytokine profile produced by peripheral blood mononuclear cells (PBMC) in response to leishmania antigens and the ability of interleukin-10 (IL-10) and transforming growth factor ß (TGF-ß) to modulate the immune response were evaluated in 21 mucosal leishmaniasis patients. Patients with mucosal disease exhibited increased gamma interferon (IFN-{gamma}) and tumor necrosis factor alpha (TNF-{alpha}) secretion and decreased IL-10 secretion compared to patients with classical cutaneous leishmaniasis. CD4+ Th1 cells were the main source of IFN-{gamma} and TNF-{alpha} production in mucosal leishmaniasis patients. Evaluation of cytokine gene expression in PBMC of these patients showed that there was strong up-regulation of IFN-{gamma} transcripts upon stimulation with leishmania antigen, in contrast to the baseline levels of IL-10 mRNA. IL-10 suppressed IFN-{gamma} production by 48% in cell cultures from cutaneous leishmaniasis patients and by 86% in cell cultures from healthy subjects stimulated with purified protein derivative, whereas in similar conditions IL-10 suppressed IFN-{gamma} production by 19% in cell cultures from mucosal leishmaniasis patients stimulated with leishmania antigen. TGF-ß suppressed IFN-{gamma} levels to a greater extent in healthy subjects than in mucosal leishmaniasis and cutaneous leishmaniasis patients. These data indicate that a poorly modulated T-cell response in mucosal leishmaniasis patients leads to production of high levels of proinflammatory cytokines, such as IFN-{gamma} and TNF-{alpha}, as well as a decreased ability of IL-10 and TGF-ß to modulate this response. These abnormalities may be the basis for the pathological findings observed in this disease.

* Corresponding author. Mailing address: Serviço de Imunologia/HUPES/Rua João das Botas s/n, Canela, 40110-160, Salvador, Bahia, Brazil. Phone: (5571) 237-7353. Fax: (5571) 245-7110. E-mail: edgar{at}ufba.br or imuno{at}ufba.br.

Editor: W. A. Petri, Jr.

Infection and Immunity, December 2002, p. 6734-6740, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6734-6740.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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