Tawfeek G M, Oteifa N M, Mustafa M A
Department of Parasitology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
J Egypt Soc Parasitol. 2001 Dec;31(3):853-66.
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.
通过每天给每只小鼠腹腔注射0.1毫升醋酸氢化可的松（25毫克/毫升）诱导实验性慢性弓形虫病的再激活。从抑制后2天开始，每周一次给予克林霉素（口服5毫克/千克）、重组白细胞介素-12（腹腔注射0.25微克）或两者联合使用，疗程为3个月。通过测定生存率和脑囊肿计数，并在抑制后的不同时间点对脑切片进行组织病理学检查，评估这些药物方案对干扰素γ（IFN-δ）产生的影响，以此来评估预防效果。所有未经治疗的免疫受损小鼠脑囊肿负担增加，IFN-δ产生减少，并死于弓形虫性脑炎。克林霉素和重组白细胞介素-12均不能预防慢性感染的再激活，不过观察到生存时间略有延长。同时给予克林霉素和重组白细胞介素-12可使73.3%的小鼠在实验结束前预防再激活。联合用药方案产生的IFN-δ水平明显高于单独使用任何一种药物，这表明重组白细胞介素-12和克林霉素可能通过增强IFN-δ的产生而发挥相加或协同作用，以预防弓形虫慢性感染的再激活。
