THE CACHEXIA ASSOCIATED WITH TRYPANOSOMA-CRUZI ACUTE INFECTION IN MICE IS ATTENUATED BY ANTI-TNF-ALPHA, BUT NOT BY ANTI-IL-6 OR ANTI-IFN-GAMMA ANTIBODIES

BALB/c male mice acutely infected with Trypanosoma cruzi underwent a s evere weight loss (around 20%, from day 18 to 31 post-infection), when compared to age-matched uninfected animals. Though mice regained weig ht later, when blood parasites were hardly detectable, wasting extende d over the chronic phase of infection. The onset and the magnitude of weight loss were related to the mouse susceptibility to infection, sin ce they were respectively earlier and higher in male mice which will d ie than in surviving ones, in males than in females, and in BALB/c tha n in B6D2 [(C57B1/6 x DBA/2)F1], a mouse strain more resistant to infe ction. Fat weight of infected mice (male BALB/c) was reduced by 60 to 80%, whereas lean mass was unaffected and water content rose by 6 to 1 0% in acute and chronic infection. Haematocrit was also decreased by 1 5-16% in acute infection. Animals failed to compensate their energetic loss since their food intake remained similar to that of uninfected a nimals. Injections of neutralizing anti-TNF-alpha monoclonal antibody into infected male mice, during the first two weeks but not later in i nfection, significantly attenuated the weight loss. Early administrati on of anti-IL-6 or anti-IFN-gamma MoAbs did not improve the mouse wast ing. Taken together, these data show that TNF is a key agent of cachex ia occurring in the acute T. cruzi infection in mice.