Inhibition of murine malaria (Plasmodium chabaudi) in vivo by recombinant interferon-gamma or tumor necrosis factor, and its enhancement by butylated hydroxyanisole.
Cell-mediated immunity to malaria may involve macrophages, the monokines that mediate endotoxicity, and reactive oxygen species. Since interferon-gamma activates macrophages to release reactive oxygen species, and tumor necrosis factor-alpha (TNF-alpha) helps both to mediate endotoxicity and to induce leukocytes to secrete reactive oxygen, we monitored the effects of administering recombinant forms of these cytokines on Plasmodium chabaudi adami infections in mice. We also fed infected mice a diet containing 0.75% butylated hydroxyanisole, a scavenger of free radicals. Infections were suppressed by daily i.p. injections of 5 x 10(4) U of recombinant mouse interferon-gamma from day -1 or by recombinant human TNF released from i.p. osmotic pumps at the rate of 6 x 10(3) U/hr. Degenerate intraerythrocytic parasites (crisis forms) were evident much sooner in the course of the suppressed infections, and parasitemias fell correspondingly earlier. The butylated hydroxyanisole diet, in contrast, enhanced the infections. In these mice crisis forms were seen later, and at higher parasitemias, than they normally occur. These observations are consistent with the concept that T cell-dependent, macrophage-derived mediators are central to the type of malarial immunity that kills parasites inside circulating red cells. They also suggest, but do not prove, that both TNF and reactive oxygen species are involved, and that the role of TNF may be more indirect, although no less important, than that of reactive forms of oxygen.
D000284:Administration, Oral; D000818:Animals; D002083:Butylated Hydroxyanisole / Q000008:administration & dosage / Q000494:pharmacology*; D004912:Erythrocytes / Q000469:parasitology; D005609:Free Radicals; D007111:Immunity, Cellular / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008288:Malaria / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D015846:Monokines; D010100:Oxygen / Q000378:metabolism*; D010961:Plasmodium / Q000187:drug effects / Q000302:isolation & purification; D011506:Proteins / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005609:Free Radicals; D015846:Monokines; D011506:Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002083:Butylated Hydroxyanisole; D007371:Interferon-gamma; D010100:Oxygen