Chagas' disease: enhancement of systemic inflammatory reaction in cyclophosphamide treated mice

An explanation was sought for the fact that an enhancement of myocarditis occurs when Trypanosoma cruzi infected mice is treated with cyclophosphamide (CY). Several schedules were tested in mice and two polar models were achieved--one presenting parasite exacerbation without inflammatory reaction and the other presenting only cellular infiltrate in function of timing and different dosage of drug. In those receiving the drug after infection, an enhancement of the parasite load was detected and it was associated with an inflammatory reaction when mice were treated every other day with low doses of CY (3 mg/kg), but such inflammation was not present if a single dose of 200 mg/kg was used 5 days after infection. On the other hand, in schedules using 200 mg/kg of CY 2 days before infection an enhancement of myocarditis was observed on day 12 post infection, but this was not associated with parasite proliferation. Finally when employing a single intermediate dose of 40 mg/kg, a parasite load as well as a myocarditis enhancement was observed. A correlation between blood monocytes rebound and the intensity of myocarditis has been observed, and the varying time of drug injection suggested that this cellular infiltrate modulates the parasite load. If the immunosuppressive period of the drug occurred during parasite tissue invasion, parasite load amplification would occur without myocarditis. This was achieved using a single dose (200 mg/kg) of CY five days after infection, since monocytosis occurs 7-8 days after drug injection, allowing for parasite multiplication in tissues. The present data bring a strong suggestion that the modulation of myocarditis and parasite load are directly correlated with the leukocytes rebound occurring after the depression period promoted by CY treatment.