Prophylactic efficacy of recombinant IL-12, clindamycin alone or in combination against experimental reactivated...

Reactivation of experimental chronic toxoplasmosis was induced by daily i.m. injection of 0.1 ml hydrocortisone acetate (25 mg/ml) per mouse. Administration of clindamycin (5 mg/kg orally), rIL-12 (0.25 microg i.p.) or combination of both was done once weekly for 3 months course starting 2 days post suppression. The prophylactic effect was assessed by determination of both survival rate and brain cyst counts with histopathological examination of brain sections at different time points post suppression besides the influence of these drug regimens on interferon gamma (IFN-delta) production. All immunocompromised untreated mice exhibited increased brain cyst burdens and reduced IFN-delta production and died due to toxoplasmic encephalitis. Neither clindamycin nor rIL-12 prevented reactivation of chronic infection, however, the slight prolongation of survival was observed. Simultaneous administration of clindamycin and rIL-12 resulted in prevention of reactivation in 73.3% of the mice till the end of the experiment. The combination regimen produced significant higher levels of IFN-delta than either drug alone suggesting that both rIL-12 and clindamycin can act additively or synergistically to prevent reactivation of chronic infection with T. gondii most probably through enhancement of IFN-delta production.