In vivo effect of anti-TNF agent (etanercept) in reactivation of latent toxoplasmosis.

ABSTRACT

Toxoplasma gondii (T. gondii), an intracellular parasite, establishes a chronic infection by forming cysts preferentially in the brain. TNF-α plays an important role in controlling the infection caused by this protozoan. Thus, the blockade of TNF-α could cause reactivation of latent toxoplasmosis infection as well as increase the risk of acute toxoplasmosis. This study evaluated the effect of etanercept, a TNF-α antagonist in reactivation of latent toxoplasmosis compared to the therapeutic effect of sulfadiazine and pyrimethamine in combination on the progress of the disease. A total of 40 laboratory-bred Swiss albino mice were infected with Me49 strain of T. gondii and divided into four groups infected control group; treated group with sulfadiazine and pyrimethamine; treated group with etanercept and treated group with both etanercept and sulfadiazine and pyrimethamine. The mean number and size of tissue cysts in brain smears of mice of each group were determined and also, serum levels of TNF-α were assessed in different study groups by an enzyme linked immunosorbent assay. The results showed that the mean TNF-α level was significantly different in the treated groups compared to that in infected control group. The highest level of TNF-α was found in the infected controls. After treatment with etanercept alone or combined with sulfadiazine and pyrimethamine, it was significantly decreased. In this study, reactivation of latent toxoplasmosis was observed by a significant increase in the mean number and sizes of Toxoplasma tissue cysts in brains of mice with established chronic toxoplasmosis after treatment with etanercept alone or combined with conventional treatment compared to both untreated chronically infected controls and infected mice treated with sulfadiazine and pyrimethamine. It was concluded that etanercept, a TNF-α antagonist may play a role in reactivation of latent toxoplasmosis. So, serological screening for toxoplasmosis might offer a valuable aid for patients treated with this drug.