The schistosomulicidal activity and the production of IL-1 and TNF-alpha by peritoneal macrophages from infected mice and their potentiation by muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) treatment.
Production of TNF-alpha and IL-1 by adherent peritoneal exudate macrophages (APEM) was monitored for 20 weeks in Schistosoma mansoni infected mice in comparison to their schistosomulicidal activity. LPS-triggered IL-1 and TNF-alpha production by APEM peaked 10 weeks post infection (p.i.) and declined thereafter. The schistosomulicidal activity of APEM also peaked after 10 weeks but remained elevated thereafter. Infected mice were also treated with the immunostimulator liposomal muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) 6 or 10 weeks p.i., and their APEM were tested 4 weeks later. APEM from such treated animals showed elevated IL-1 and TNF-alpha production when treatment commenced 6 weeks p.i., while their schistosomulicidal activity increased when treatment commenced either 6 or 10 weeks p.i. The L-arginine inhibitor, NG monomethyl arginine, markedly inhibited the schistosomulicidal activity but not the IL-1 and TNF-alpha production of APEM. Our results show that monokine production increases during the acute phase of infection and declines during its chronic phase, while macrophage schistosomulicidal activity remains constant throughout. Furthermore, TNF-alpha or IL-1 may play a minor role in APEM mediated killing of schistosomula.
Seger
M
M
Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Gold
D
D
Lengy
J
J
Pauli
H
H
Keisari
Y
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001681:Biological Assay; D002478:Cells, Cultured; D004337:Drug Carriers; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010537:Peritoneum / Q000166:cytology; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D019323:omega-N-Methylarginine
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D007375:Interleukin-1; D007376:Interleukin-2; D008081:Liposomes; D010714:Phosphatidylethanolamines; D014409:Tumor Necrosis Factor-alpha; C037144:mifamurtide; D019323:omega-N-Methylarginine; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D001120:Arginine