Serum containing tumor necrosis factor is cytotoxic for the human malaria parasite Plasmodium falciparum.
Sera (BCG-lipopolysaccharide [LPS] serum) were obtained from mice infected with Mycobacterium bovis BCG 2 h after intravenous administration of bacterial endotoxin (LPS). Varying concentrations of sera were added to cultures of Plasmodium falciparum-infected human erythrocytes; parasite viability was assessed by hypoxanthine incorporation after 4 days in culture. At concentrations of 1 to 3%, cultures treated with BCG-LPS serum showed a two- to threefold increase in hypoxanthine incorporation; at higher concentrations (4 to 8%), hypoxanthine incorporation fell to 2 to 5% of that in control cultures. Concurrent assays with control sera (from untreated mice or mice treated with BCG or LPS alone) caused some stimulation but no inhibition at up to 8% concentration. Examination of cultures treated with BCG-LPS serum showed morphological, deterioration of parasites within erythrocytes. The presence of tumor necrosis factor in the BCG-LPS serum was confirmed by using a standard L-cell cytotoxicity assay. In addition, rabbit antiserum against partially purified tumor necrosis factor protected intraerythrocytic forms of P. falciparum from the toxic effects of BCG-LPS serum. These data suggest that the factor in BCG-LPS serum that is toxic to P. falciparum in human erythrocytes is antigenically similar or identical to tumor necrosis factor. This nonantibody mediator of killing may play a role in human malaria.
D000818:Animals; D002460:Cell Line; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000276:immunology; D006131:Growth Inhibitors / Q000097:blood*; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009164:Mycobacterium Infections / Q000097:blood; D009163:Mycobacterium bovis; D010963:Plasmodium falciparum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D006131:Growth Inhibitors; D007042:Hypoxanthines; D007106:Immune Sera; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019271:Hypoxanthine