Potential role of rolipram, a specific phosphodiestrase inhibitor, in preventing the establishment of a chronic state of toxoplasma gondii infection

ABSTRACT

Progression to a chronic state of the disease after an initial, mostly asymptomatic, acute phase is the normal fate of Toxoplasma gondii infection in immunocompetent hosts. Parasite reactivation of established chronic stage has serious manifestations on immunocompromised hosts. Tumor necrosis factor [TNF]- alpha, Interleukin [IL]-12 and cAMP have pivotal roles in tachyzoite to bradyzoite conversion and establishment of a chronic state of the disease. Rolipram, a specific phosphodiestrase inhibitor, has different regulatory roles on these factors. A daily oral dose of 10 mg/kg of rolipram was given to a group of mice, one week after T. gondii infection and for three weeks. Rolipram was found to have a great impact in preventing progression of chronic state and in mitigation of the pathology of this stage. Toxoplasma gondii tissue cyst load in mice brains has showed almost 4-fold reduction with the use of rolipram. The drug also mitigated the inflammation and pathologic processes in liver and more evident in the brain. Anti-Toxoplasma antibody titers are also significantly reduced in rolipram-treated group