Cytokine control of the granulomatous response in Schistosoma mansoni-infected baboons: Role of exposure and treatment

Variations in exposure and treatment may contribute to heterogeneity in imm unity and granuloma-induced pathology in human schistosomiasis, To examine this hypothesis, olive baboons were either repeatedly infected with Schisto soma mansoni cercariae or received an equivalent dose in a single infection . They were then cured with praziquantel and reinfected with a single expos ure. Serial liver biopsies were obtained throughout the course of the exper iment, and cytokine responses by peripheral blood mononuclear cells were me asured every 2 to 3 weeks. Reinfection after treatment resulted in a two-fo ld-smaller granuloma size at 6 and 9 weeks after infection compared to the size for the same period after primary infection (P < 0.001) but had no eff ect at 16 or 19 weeks postinfection. The pattern of exposure did not influe nce granuloma size. During primary infection schistosome-soluble egg antige n (SEA)-induced cytokine production correlated with granulomatous inflammat ion. Cytokine levels peaked during the acute infection, declined with chron ic infection, and became undetectable after treatment, Reinfection after tr eatment stimulated a two- to three fold increase in SEA-specific interleuki n-4 (IL-4), IL-5, IL-10, IL-2, and transforming growth factor P (TGF-P) pro duction and a marked rise in SEA-specific immunoglobulin E (IgE) and IgG re gardless of the type of exposure. Cytokine production was significantly gre ater in repeatedly exposed animals (P < 0.001), SEA-induced gamma interfero n production, however, did not increase with reinfection after treatment. S EA-induced TGF-P was the only cytokine that remained elevated as the infect ion become chronic and correlated with diminished hepatic granuloma size, i mplying its participation in down-modulation. These studies demonstrate tha t baboons partially retain their ability to down-modulate the granulomatous response after treatment.