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

ABSTRACT

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.