cgp-20376 and Granuloma

Resistance of BALB/c mice to infective third-stage larvae (L3) of the human filarial parasite Brugia malayi is thymus-dependent, although the actual effector mechanisms that mediate larval killing are unknown. The present study examined the effect of carrageenan (CGN) on the mechanisms of resistance to B. malayi infection in heterozygous (nu/+) and nude (nu/nu) mice. Mice were treated with CGN at a single dose of 20 or 200 mg/kg and were inoculated intraperitoneally 1 day later with 100 L3. The results showed a dose-dependent increase in the numbers of L4 and L5 that were recovered from nu/+ and nu/nu mice. CGN treatment also enhanced the recovery of mature adult worms from nu/nu mice and appeared to abolish partially the dichotomy of resistance between the usually more susceptible male and the more resistant female nu/nu mouse. Microfilariae were found in the peripheral blood and the peritoneal cavity of CGN-treated male and female nu/nu mice and in the peritoneal cavity of male but not female nu/+ mice. Fewer larval granulomas were recovered from the peritoneal cavity of treated mice. CGN-treated, parasitized nu/+ and nu/nu mice showed high titers of IgM and IgG antibodies. An experimental compound, CGP 20376, showed 100% larvicidal activity following the administration of a single dose of 20 mg/kg to CGN-treated mice. From this study, we conclude that macrophages alone or in conjunction with other cells are actively involved in the resistance of mice to B. malayi L3.

Topics: Animals; Antibodies, Helminth; Brugia; Carrageenan; Elephantiasis, Filarial; Female; Filaricides; Granuloma; Immunity, Cellular; Immunosuppression Therapy; Macrophages; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Microfilariae; Peritoneal Cavity; Thiazoles