Effects of interleukin-4 deprivation and treatment on resistance to Trypanosoma cruzi.
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.
Abrahamsohn
I A
IA
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-900, SP, Brazil. iabraham@usp.br
da Silva
A P
AP
Coffman
R L
RL
D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000276:immunology / Q000627:therapeutic use; D015847:Interleukin-4 / Q000276:immunology* / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000276:immunology*
D016207:Cytokines; D011994:Recombinant Proteins; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma