Morihiro Saito

Induction of tumor necrosis factor α and nitric oxide in rabbits inoculated with a cyst extract of Sarcocystis cruzi

Rabbits develop a toxic reaction similar to endotoxemia following inoculation with a Sarcocystis cruzi cyst extract. To analyze the pathophysiology of the reaction, serum tumor necrosis factor alpha (TNFalpha), nitric oxide (NO) and lipid-lipoprotein profiles were investigated in rabbits given the cyst extract and lipopolysaccharide (LPS) by subcutaneous inoculation. In animals given the cyst extract, overproduction of TNFalpha was detected, together with an increase in NO. The animals developed derangement of lipid metabolism, which was considered to have resulted from TNFalpha induction, consisting of elevated triglyceride and very low density lipoprotein levels and decreased high density lipoprotein (HDL) levels. Serum interleukin-6-like activity also increased transiently in the animals. Capability of the cyst extract to induce TNFalpha, NO and the lipid profile derangement were completely lost by boiling. In animals given LPS, TNFalpha was induced and HDL decreased moderately, without inactivation of those activities of LPS by boiling. These results indicated that S. cruzi cyst extract is a potent, but thermolabile inducer of TNFalpha and NO for rabbits. It is likely that TNFalpha and NO play important roles as mediators in the reaction associated with toxicity of the cyst extract in rabbits.