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Infection and Immunity, April 2000, p. 1975-1979, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Effects of Interleukin-4 Deprivation and Treatment on Resistance to Trypanosoma cruzi

Ises A. Abrahamsohn,1,* Ana Paula Galvão da Silva,1,dagger and Robert L. Coffman2

Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-900, SP, Brazil,1 and DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 943032

Received 11 October 1999/Returned for modification 13 December 1999/Accepted 7 January 2000

Trypanosoma cruzi (Y strain)-infected interleukin-4-/- (IL-4-/-) mice of strains 129/J, BALB/c, and C57BL/6 showed no significant difference in parasitemia levels or end point mortality rates compared to wild-type (WT) mice. Higher production of gamma interferon (IFN-gamma ) by parasite antigen (Ag)-stimulated splenocytes was observed only for C57BL/6 IL-4-/- mice. Treatment of 129/J WT mice with recombinant IL-4 (rIL-4), rIL-10, anti-IL-4, and/or anti-IL-10 monoclonal antibodies (MAbs) did not modify parasitism. However, WT mice treated with rIL-4 and rIL-10 had markedly increased parasitism and suppressed IFN-gamma synthesis by spleen cells stimulated with parasite Ag, concanavalin A, or anti-CD3. Addition of anti-IL-4 MAbs to splenocyte cultures from infected WT 129/J, BALB/c, or C57BL/6 mice failed to modify IFN-gamma synthesis levels; in contrast, IL-10 neutralization increased IFN-gamma production and addition of rIL-4 and/or rIL-10 diminished IFN-gamma synthesis. We conclude that endogenous IL-4 is not a major determinant of susceptibility to Y strain T. cruzi infection but that IL-4 can, in association with IL-10, modulate IFN-gamma production and resistance.

* Corresponding author. Mailing address: Departamento de Imunologia, ICB/USP, Av. Prof. Lineu Prestes 1730, 05508-900 São Paulo, SP, Brazil. Phone: 55-11-818-7383. Fax: 55-11-818-7224. E-mail: iabraham{at}usp.br.

dagger Present address: Departamento de Patologia, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil.

Infection and Immunity, April 2000, p. 1975-1979, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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