Thymocyte depletion during acute Trypanosoma cruzi infection in C57BL/6 mice is partly reverted by lipopolysaccharide pretreatment

ROGGERO E; PIAZZON I; NEPOMNASCHY I; PEREZ A; VELIKOVSKY A; REVELLI S; BOTTASSO O; BOTTASSO OSCAR

FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Glasgow; Año: 2004 vol. 41 p. 123 - 131

0928-8244

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-aÞ. Because this situation may result from an excessive inflammatory syndrome, mice were now given anti-TNF-a mAbs throughout their acute infection, or subjected to a LPS desensitization protocol before parasite challenge. Treatment with anti-TNF-a 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-a 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-a and IL-6 serum concentrations, and CD4þ CD8þ thymocyte loss. LPS pretreatment allowed a better infection control and protected from the accompanyingtissue damage.