PMID- 10569776 OWN - NLM STAT- MEDLINE DCOM- 19991220 LR - 20210526 IS - 0019-9567 (Print) IS - 1098-5522 (Electronic) IS - 0019-9567 (Linking) VI - 67 IP - 12 DP - 1999 Dec TI - Cytokine control of the granulomatous response in Schistosoma mansoni-infected baboons: role of exposure and treatment. PG - 6565-71 AB - Variations in exposure and treatment may contribute to heterogeneity in immunity and granuloma-induced pathology in human schistosomiasis. To examine this hypothesis, olive baboons were either repeatedly infected with Schistosoma mansoni cercariae or received an equivalent dose in a single infection. They were then cured with praziquantel and reinfected with a single exposure. Serial liver biopsies were obtained throughout the course of the experiment, and cytokine responses by peripheral blood mononuclear cells were measured every 2 to 3 weeks. Reinfection after treatment resulted in a twofold-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 effect at 16 or 19 weeks postinfection. The pattern of exposure did not influence granuloma size. During primary infection schistosome-soluble egg antigen (SEA)-induced cytokine production correlated with granulomatous inflammation. Cytokine levels peaked during the acute infection, declined with chronic infection, and became undetectable after treatment. Reinfection after treatment stimulated a two- to three-fold increase in SEA-specific interleukin-4 (IL-4), IL-5, IL-10, IL-2, and transforming growth factor beta (TGF-beta) production and a marked rise in SEA-specific immunoglobulin E (IgE) and IgG regardless of the type of exposure. Cytokine production was significantly greater in repeatedly exposed animals (P < 0.001). SEA-induced gamma interferon production, however, did not increase with reinfection after treatment. SEA-induced TGF-beta was the only cytokine that remained elevated as the infection become chronic and correlated with diminished hepatic granuloma size, implying its participation in down-modulation. These studies demonstrate that baboons partially retain their ability to down-modulate the granulomatous response after treatment. FAU - Mola, P W AU - Mola PW AD - Division of Infectious Diseases, Institute of Primate Research, National Museums of Kenya, Karen, Nairobi, Kenya. FAU - Farah, I O AU - Farah IO FAU - Kariuki, T M AU - Kariuki TM FAU - Nyindo, M AU - Nyindo M FAU - Blanton, R E AU - Blanton RE FAU - King, C L AU - King CL LA - eng GR - AI01202/AI/NIAID NIH HHS/United States GR - AI35935/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Antibodies, Helminth) RN - 0 (Antigens, Helminth) RN - 0 (Cytokines) RN - 0 (Immunoglobulin G) RN - 0 (Schistosomicides) RN - 37341-29-0 (Immunoglobulin E) RN - 6490C9U457 (Praziquantel) SB - IM MH - Animals MH - Antibodies, Helminth/blood MH - Antigens, Helminth/immunology MH - Cytokines/biosynthesis/*immunology MH - Disease Models, Animal MH - Feces/parasitology MH - Granuloma/*pathology MH - Immunoglobulin E/blood MH - Immunoglobulin G/blood MH - Liver/pathology MH - Liver Diseases, Parasitic/drug therapy/parasitology/*pathology MH - Male MH - Papio MH - Parasite Egg Count MH - Praziquantel/therapeutic use MH - Schistosoma mansoni/growth & development/*immunology MH - Schistosomiasis mansoni/drug therapy/parasitology/*pathology MH - Schistosomicides/therapeutic use PMC - PMC97068 EDAT- 1999/11/24 00:00 MHDA- 1999/11/24 00:01 PMCR- 1999/12/01 CRDT- 1999/11/24 00:00 PHST- 1999/11/24 00:00 [pubmed] PHST- 1999/11/24 00:01 [medline] PHST- 1999/11/24 00:00 [entrez] PHST- 1999/12/01 00:00 [pmc-release] AID - 0987 [pii] AID - 10.1128/IAI.67.12.6565-6571.1999 [doi] PST - ppublish SO - Infect Immun. 1999 Dec;67(12):6565-71. doi: 10.1128/IAI.67.12.6565-6571.1999.