Malaria antigen and cytokine-induced production of reactive nitrogen intermediates by murine macrophages: no relevance to the development of experimental cerebral malaria.
The in vitro production of reactive nitrogen intermediates (RNI) by murine macrophages was evaluated in response to heat-stable malaria antigen and cytokines. Malaria antigen, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) induced RNI production in macrophages in a dose-dependent way. RNI production steadily increased over a 2-day period and was enhanced when the malaria antigen was co-incubated with IFN-gamma and/or TNF. RNI production induced by either IFN-gamma or malaria antigen or a combination of the two was suppressed by pentoxifylline in a dose-dependent manner. Pentoxifylline did not significantly influence TNF-induced RNI production. L-N-monomethyl arginine reduced malaria antigen, IFN-gamma and TNF-induced RNI production when these reagents were used in combination or alone. An anti-TNF monoclonal antibody (mAb) reduced IFN-gamma-induced RNI production, but did not significantly alter the malaria antigen-induced RNI synthesis by macrophages. The influence of inhibitors of nitric oxide synthase, L-N-monomethyl arginine and N omega-nitro-L-arginine, was studied in experimental cerebral malaria. They did not exert any significant effect on the development of cerebral malaria in Plasmodium berghei ANKA-infected CBA/J mice.
Kremsner
P G
PG
Landesinstitut für Tropenmedizin Berlin, Germany.
Nüssler
A
A
Neifer
S
S
Chaves
M F
MF
Bienzle
U
U
Senaldi
G
G
Grau
G E
GE
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D001120:Arginine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016207:Cytokines / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D016779:Malaria, Cerebral / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009584:Nitrogen / Q000378:metabolism*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019323:omega-N-Methylarginine
D000953:Antigens, Protozoan; D016207:Cytokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D007371:Interferon-gamma; D001120:Arginine; D009584:Nitrogen