Immunoregulation in experimental murine Trypanosoma congolense infection: anti-IL-10 antibodies reverse trypanosome-mediated suppression of lymphocyte proliferation in vitro and moderately prolong the lifespan of genetically susceptible BALB/c mice.
We infected highly susceptible BALB/c and relatively resistant C57BL/6 mice with cloned Trypanosoma congolense and followed the effects of these infections on the circulating parasite numbers, mouse mortality and cytokine expression. C57BL/6 mice controlled their parasitaemia and survived for up to 163 +/- 12 days, while BALB/c mice could not control their parasitaemia and succumbed to the infection within 8.4 +/- 0.5 days. Susceptible BALB/c mice had dramatically higher plasma levels of IL-10 than the resistant C57BL/6 mice from day 7 forward. This was preceded by an earlier and higher level induction of splenic IL-10 messenger RNA (mRNA) expression in the infected BALB/c mice. There was a strong negative correlation between the splenocyte proliferative responses to Concanavalin-A (Con-A) and their production of IL-10 in these infected BALB/c mice. Co-treatment of the Con-A-stimulated spleen cell cultures with monoclonal anti-IL-10 antibodies, but not isotype-matched control antibodies, could completely reverse this suppression of the splenocyte proliferative response. Finally, in three experiments, anti-IL-10 antibody treatment in vivo reduced the peak circulating parasitaemia of infected BALB/c mice by 43% and increased their median survival periods by 38% relative to isotype-matched control antibody-treated mice.
Uzonna
J E
JE
Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Canada.
Kaushik
R S
RS
Gordon
J R
JR
Tabel
H
H
D000818:Animals; D004133:Diminazene / Q000031:analogs & derivatives / Q000627:therapeutic use; D004198:Disease Susceptibility; D005260:Female; D016753:Interleukin-10 / Q000276:immunology*; D008017:Life Expectancy; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014344:Trypanocidal Agents / Q000627:therapeutic use; D014348:Trypanosoma congolense / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000276:immunology*
D014344:Trypanocidal Agents; D016753:Interleukin-10; C003915:diminazene aceturate; D004133:Diminazene