title: Analysis of cytokine mRNA expression during primary granuloma formation induced by eggs of Schistosoma mansoni.
abstract: Granulomas induced by parasite eggs are the primary lesions in mice infected with Schistosoma mansoni. Temporal analysis of cytokine mRNA expression in lung tissue containing synchronized granulomas demonstrated a Th0-like pattern of lymphokine expression. IFN-gamma, IL-1 beta, and IL-6 were the primary cytokines induced by day 1 in developing lung granulomas initiated by i.v. egg injection. These changes were followed by increases in expression of IL-2, IL-4, and IL-10 mRNA on day 3 and TNF-alpha and IL-5 mRNA on day 6. Nearly all cytokine mRNA reached maximal levels by day 6, which preceded the peak in granuloma size seen on day 14. In vivo treatment of egg-injected mice with either anti-IL-2 or anti-IL-4 antibodies significantly diminished the size of circumoval granulomas in the lungs. Both groups of antibody-treated animals displayed a marked reduction in IL-4 as well as IL-5 mRNA expression, although IFN-gamma and IL-2 mRNA levels were unchanged or slightly increased. These findings confirm previous observations suggesting a role for IL-2 in egg-induced pathology via the generation of Th2-associated responses, and also indicate a primary function for IL-4 in granuloma formation. Analysis of responses after injection of eggs into nude mice demonstrated that only the Th2 cytokines IL-4 and IL-5 are exclusively dependent on T cells for their induction. Taken together, these data suggest that Th2 cells producing IL-4 play a major role in egg granuloma formation, and that the induction and ultimate down-modulation of Th2-like responses may be influenced by non-T-cell-derived cytokines.
authors.affiliation: Immunology and Cell Biology Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
authors.forename: T A
authors.initials: TA
authors.lastname: Wynn
authors.forename: I
authors.initials: I
authors.lastname: Eltoum
authors.forename: A W
authors.initials: AW
authors.lastname: Cheever
authors.forename: F A
authors.initials: FA
authors.lastname: Lewis
authors.forename: W C
authors.initials: WC
authors.lastname: Gause
authors.forename: A
authors.initials: A
authors.lastname: Sher
mesh_terms: D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010063:Ovum / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger