TY - JOUR T1 - Treatment with Liposome-Bound Recombinant Human Tumor Necrosis Factor-α Suppresses Parasitemia and Protects against<em>Plasmodium berghei</em> k173-Induced Experimental Cerebral Malaria in Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 114 LP - 120 VL - 288 IS - 1 AU - N. S. Postma AU - D. J. A. Crommelin AU - W. M. C. Eling AU - J. Zuidema Y1 - 1999/01/01 UR - http://jpet.aspetjournals.org/content/288/1/114.abstract N2 - Our study describes liposomes (conventional or sterically stabilized) as carrier systems for recombinant human tumor necrosis factor-α (rhTNF-α) to increase its protective efficacy againstPlasmodium berghei-induced experimental cerebral malaria (ECM) in mice. rhTNF-α was either covalently coupled to the outer surface of preformed liposomes or encapsulated into the liposomes. For coupling to the liposomes, reactive thiol groups were introduced in rhTNF-α by reaction with N-succinimidylS-acetylthioacetate. Intravenous injection of liposome-bound rhTNF-α substantially enhanced protection against ECM as compared with injection of free rhTNF-α. A similar protective efficacy against ECM was obtained by treatment with rhTNF-α coupled to either conventional or sterically stabilized liposomes. Encapsulation of rhTNF-α into liposomes did not improve the protective efficacy of rhTNF-α against P. berghei-induced ECM. Parasitemia was suppressed by treatment with either free or liposome-bound rhTNF-α in mice protected against ECM, but not in rhTNF-α-treated mice developing ECM. These data suggest that the effect of rhTNF-α on parasitemia plays a role in establishing protection against ECM. Our studies indicate that liposome-bound rhTNF-α exhibits an enhanced protective efficacy against ECM compared with free rhTNF-α. It is hypothesized that thiolation of rhTNF-α and coupling to the liposomal bilayer stabilizes the bioactive trimeric configuration of rhTNF-α. The American Society for Pharmacology and Experimental Therapeutics ER -