Thymocyte depletion during acute Trypanosoma cruzi infection in C57BL/6 mice is partly reverted by lipopolysaccharide pretreatment.
Infection with Trypanosoma cruzi in C57BL/6 mice leads to a progressive fatal disease accompanied by thymocyte depletion, which is not related with a higher parasite burden but with increased serum levels of tumour necrosis factor alpha (TNF- alpha). Because this situation may result from an excessive inflammatory syndrome, mice were now given anti-TNF-alpha mAbs throughout their acute infection, or subjected to a LPS desensitization protocol before parasite challenge. Treatment with anti-TNF-alpha mAbs failed to ameliorate thymocyte depletion but shortened survival time and increased parasite load. Pretreatment with LPS (desensitization followed by a sublethal LPS dose) prolonged survival time with a trend to reduce parasitemias and TNF-alpha serum concentrations. Given that pentoxifylline (PTx) interferes with in vitro LPS tolerance, experiments by administering PTx in combination with the tolerance-inducing LPS doses were also performed. Such schedule significantly reduced mortality, TNF-alpha and IL-6 serum concentrations, and CD4+ CD8+ thymocyte loss. LPS pretreatment allowed a better infection control and protected from the accompanying tissue damage.
Roggero
Eduardo
E
Instituto de Inmunología, Facultad de Ciencias Médicas de Rosario, Argentina.
Piazzon
Isabel
I
Nepomnaschy
Irene
I
Perez
Ana
A
Velikovsky
Alejandro
A
Revelli
Silvia
S
Bottasso
Oscar
O
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology; D005434:Flow Cytometry; D006321:Heart / Q000469:parasitology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D010431:Pentoxifylline / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D010431:Pentoxifylline