Effect of chemotherapeutic treatment on cytokine (IFN-γ, IL-2, IL-4, IL-5, IL-10) gene transcription in response to specific antigens in Brugia malayi-infected Mastomys coucha

Abstract

Cytokine (interferon (IFN)-gamma, interleukin (IL)-2, IL-4, IL-5, IL-10) gene transcription in response to filarial antigens was determined in peripheral blood mononuclear cells of Brugia malayi-infected Mastomys coucha in the course of untreated and chemotherapeutically abbreviated infections. Transcript levels in infected untreated animals suggest particular time courses for the various cytokines with ongoing parasite development and differing efficacies of female, male, microfilarial, and L3 antigens in inducing cytokine gene transcription. Gene transcription of both of Th1- and Th2-associated cytokines were initiated in the course of the infection in a manner that does not fit in a simple Th1-Th2 paradigm. IFN-gamma and IL-4 gene transcripts prevailed during prepatency. In case of the other cytokine genes considered in the study, transcription in general peaked around beginning of patency. During the phase of increasing microfilaremia (approximately 120-180 days p. i.) cytokine gene transcription was generally decreased. Later on, when the parasitemia had leveled off, except IFN-gamma, transcript levels often tended to increase. In chemotherapeutically treated animals, the outcome varied with the different efficacies of the drugs employed. The highly microfilaricidal cyclodepsipeptide BAY 44-4400 eliminated circulating microfilariae and partially sterilized adult worms without killing them. This kind of treatment hardly affected cytokine responses. In contrast, the therapy with Flubendazole, a selectively macrofilaricidal benzimidazole, and particularly the application of CGP 20376, a highly efficient microfilaricidal and macrofilaricidal benzthiazole, resulted in enhanced transcription of the Th1-associated IFN-gamma and IL-2 genes as well as of the Th2-associated IL-5 gene 2-3 months after treatment. IL-10 gene transcription seemed transiently increased after 1 month. There was no effect of any treatment on the IL-4 gene transcription.