title: In vivo cytokine profiles in patients with kala-azar. Marked elevation of both interleukin-10 and interferon-gamma.
abstract: The immunological mechanisms underlying the susceptibility to disseminated visceral parasitism of mononuclear phagocytes in patients with kala-azar remain undefined. Resistance and susceptibility are correlated with distinct patterns of cytokine production in murine models of disseminated leishmanial disease. To assess lesional cytokine profiles in patients with kala-azar, bone marrow aspirates were analyzed using a quantitative reverse transcriptase PCR technique to amplify specific mRNA sequences of multiple Th1-, Th2-, and/or macrophage-associated cytokines. Transcript levels of IL-10 as well as IFN-gamma were significantly elevated in patients with active visceral leishmaniasis; IL-10 levels decreased markedly with resolution of disease. These findings suggest that IL-10, a potent, pleiotropic suppressor of all known microbicidal effector functions of macrophages, may contribute to the pathogenesis of kala-azar by inhibiting the cytokine-mediated activation of host macrophages that is necessary for the control of leishmanial infection.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
authors.forename: C L
authors.initials: CL
authors.lastname: Karp
authors.forename: S H
authors.initials: SH
authors.lastname: el-Safi
authors.forename: T A
authors.initials: TA
authors.lastname: Wynn
authors.forename: M M
authors.initials: MM
authors.lastname: Satti
authors.forename: A M
authors.initials: AM
authors.lastname: Kordofani
authors.forename: F A
authors.initials: FA
authors.lastname: Hashim
authors.forename: M
authors.initials: M
authors.lastname: Hag-Ali
authors.forename: F A
authors.initials: FA
authors.lastname: Neva
authors.forename: T B
authors.initials: TB
authors.lastname: Nutman
authors.forename: D L
authors.initials: DL
authors.lastname: Sacks
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001853:Bone Marrow / Q000737:chemistry* / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D016753:Interleukin-10 / Q000032:analysis*; D007898:Leishmaniasis, Visceral / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000502:physiology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma