Suppression of in vitro IFN-gamma production by spleen cells of Plasmodium chabaudi-infected C57BL/10 mice exposed to dexamethasone at a low dose.
After infection with Plasmodium chabaudi, C57BL/10 mice produced significant amounts of serum IFN-gamma, developed a low level of parasitemia and survived the infection. Production of IFN-gamma was also obvious when spleen cells of the infected mice were stimulated with the parasite antigen contained in an erythrocyte lysate in vitro. Depletion of CD4+ T cells abrogated production of IFN-gamma, leading to loss of resistance to the infection. The CD4+ T cells/IFN-gamma-dependent resistance of the C57BL/10 mice against P. chabaudi was applied to assess immunotoxicological effect of dexamethasone (DEX). Administration of a high dose (0.75 mg/kg) resulted in loss of the splenic cellularity, remarkable decrease in serum IFN-gamma production, increased level of parasitemia, and eventual death of the infected mice. In contrast, DEX at a low dose (0.02 mg/kg) induced no alternation in the in vivo host immune activity and the mice survived the infection. However, when spleen cells were obtained from the infected mice administered the low dose of DEX and stimulated in vitro with the parasite antigen, a significantly decreased level of IFN-gamma was demonstrated with compared to control mice. These findings demonstrate that the in vitro production of IFN-gamma by spleen cells from P. chabaudi-resistant C57BL/10 mice was more sensitive to the immunosuppressive effect of in vivo administration of DEX. This ex vivo assay might provide a method for evaluation of drug-induced immunotoxicity at a higher sensitivity than the conventional host resistant assays such as comparison of severity of disease or time to death.
Tsutsui
N
N
Toxicology Laboratory, Yokohama Research Center, Mitsubishi Chemical Corporation, Japan.
Kamiyama
T
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis*; D008288:Malaria / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D015704:CD4 Antigens; D003907:Dexamethasone; D007371:Interferon-gamma