sq-23377 and Elephantiasis--Filarial

Humans living in areas where filariasis is endemic vary greatly in their exposure to mosquito-borne infective third-stage larvae (L3) of these parasitic helminths. Because the intensity of exposure to Ags affects T cell differentiation and susceptibility to parasitic infections in murine models, we compared T cell and cytokine responses in 97 residents of two villages in Papua New Guinea, where transmission intensity of Wuchereria bancrofti differed by 63-fold (37 vs 2355 L3 per person per year). Residents of the high transmission village had 4- to 11-fold lower proliferation and IFN-gamma responses to filarial Ags, nonparasite Ag, and PHA by PBMC compared with the low transmission village (p < 0.01) even when subjects were matched for intensity of infection. In contrast, filarial Ag-driven IL-5 production was 5.5-fold greater (p < 0.001), and plasma IL-4 and TGF-beta levels were 4-fold and 34% higher, respectively, in residents of the high transmission village. IL-4 and IL-10 responses by PBMC differed little according to village, and increased production of the counterregulatory cytokines IL-10 or TGF-beta by PBMC did not correlate with weak proliferation and IFN-gamma responses. Plasma IL-5, IFN-gamma, and IL-10 levels were similar in the two villages. These data demonstrate that the intensity of exposure to L3 affects lymphocyte responsiveness and cytokine bias possibly by a mechanism that alters APC function.

Topics: Adolescent; Adult; Animals; Child; Cytokines; Elephantiasis, Filarial; Female; Humans; Immune Tolerance; Interleukin-4; Ionomycin; Lymphocyte Activation; Male; Middle Aged; Papua New Guinea; Phytohemagglutinins; Severity of Illness Index; T-Lymphocytes; Tetradecanoylphorbol Acetate; Th2 Cells; Wuchereria bancrofti

Peripheral blood eosinophil counts and serum levels and in vitro production of eosinophilopoietic cytokines were assessed before and at frequent intervals after diethylcarbamazine treatment of Bancroftian filariasis. Eosinophil counts peaked at day 7 after the start of treatment (359% +/- 118% of pretreatment levels) and declined to pretreatment levels by day 17. Serum interleukin (IL)-5, undetectable in 14 of 15 patients before treatment, rose sharply but transiently, with peak levels (32 +/- 7 pg/mL) 2 days after diethylcarbamazine treatment. Granulocyte-macrophage colony-stimulating factor and IL-3 were not detectable in serum at any time. In vitro mitogen-induced IL-5 levels decreased significantly in 7 of 9 patients 3 days after treatment when serum IL-5 was at near-peak levels. By day 10 IL-5 values increased in 8 of 9 patients compared with treatment values (P < .02). These data define the temporal relation between serum IL-5 levels and the subsequent development of eosinophilia and suggest that lymphocytes are the source of IL-5.

Topics: Adolescent; Adult; Diethylcarbamazine; Elephantiasis, Filarial; Eosinophilia; Eosinophils; Humans; Interleukin-5; Ionomycin; Kinetics; Male; Tetradecanoylphorbol Acetate