NONIONIC BLOCK-COPOLYMERS POTENTIATE ACTIVITIES OF DRUGS FOR TREATMENT OF INFECTIONS WITH TOXOPLASMA-GONDII

We studied the interaction between drugs and the nonionic block copoly mers CRL 8131 and CRL 8142 in the treatment of toxoplasmosis in murine models of the disease. Treatment of acute toxoplasmosis with copolyme rs alone caused slight prolongation of time to death but not survival, In contrast, significant survival occurred when mice were treated wit h either copolymer combined,vith doses of sulfadiazine, pyrimethamine, clindamycin, or atovaquone, which did not prevent mortality when used alone. Treatment with CRL 8131 plus sulfadiazine or pyrimethamine res ulted in 50 or 40% survival, respectively, Treatment with the same cop olymer plus a dose of clindamycin that protected 40% of the mice when used alone resulted in 100% survival, Treatment of toxoplasmic encepha litis with CRL 8131 plus an ineffective dose of atovaquone reduced the inflammation and numbers of Toxoplasma gondii cysts in the brain. Stu dies to investigate the drug-enhancing activity of CRL 8131 revealed t hat mice immunized with toxoplasma lysate plus copolymer had lymphocyt e proliferation responses to T.gondii antigens significantly higher th an those in mice immunized with lysate alone, Challenge of immunized m ice with a lethal inoculum of T. gondii resulted in significant surviv al. Administration of CRL 8131 alone appeared to cause a down-regulati on in the production of gamma interferon and up-regulation in the prod uction of interleukin-2. No differences were noted in the production o f tumor necrosis factor alpha between mice treated with CRL 8131 and c ontrols.