title: Effect of LACK and KMP11 on IFN-gamma production by peripheral blood mononuclear cells from cutaneous and mucosal leishmaniasis patients.
abstract: The immune modulatory properties of recombinant antigens Kinetoplasmid membrane protein-11 (KMP11) and Leishmania homologue of receptors for activated C kinase (LACK) in cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) patients were evaluated. The mean levels of interferon-gamma (IFN-gamma) in soluble leishmania antigen (SLA) stimulated peripheral blood mononuclear cells (PBMC) of ML and CL patients were 5625 +/- 2333 pg/ml and 4422 +/- 3665 pg/ml, respectively. IFN-gamma was not detected in cultures stimulated with KMP11 or LACK. Interleukin-10 (IL-10) concentration in SLA, KMP11 and LACK-stimulated PBMC of ML patients was 13 +/- 12 pg/ml, 285 +/- 388 pg/ml and 802 +/- 483 pg/ml, respectively. Addition of KMP11 or LACK to SLA-stimulated PBMC of CL and ML patients enhanced IL-10 production (P < 0.05). Addition of KMP11 decreased IFN-gamma levels by 52% in CL patients and by 19% in ML patients. Addition of LACK to SLA-stimulated cultures decreased IFN-gamma levels by 58% in CL patients and by 30% in ML patients. Neutralization of IL-10 abrogated the downregulatory effect of LACK and KMP11. The modulatory properties of LACK and KMP11 are due to induction of IL-10 production and may be helpful for attenuating chronic inflammatory diseases. However, in some clinical conditions, as demonstrated for ML, these molecules are not able to suppress the IFN-gamma response, even inducing IL-10 production.
authors.affiliation: Serviço de Imunologia, Hospital Universitário Prof Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil.
authors.forename: L P
authors.initials: LP
authors.lastname: Carvalho
authors.forename: S
authors.initials: S
authors.lastname: Passos
authors.forename: W O
authors.initials: WO
authors.lastname: Dutra
authors.forename: M
authors.initials: M
authors.lastname: Soto
authors.forename: C
authors.initials: C
authors.lastname: Alonso
authors.forename: K J
authors.initials: KJ
authors.lastname: Gollob
authors.forename: E M
authors.initials: EM
authors.lastname: Carvalho
authors.forename: A
authors.initials: A
authors.lastname: Ribeiro de Jesus
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology / Q000494:pharmacology*; D002648:Child; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D007892:Leishmania braziliensis / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D007898:Leishmaniasis, Visceral / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology*; D008875:Middle Aged; D015800:Protozoan Proteins / Q000276:immunology / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology
chemical_list: D000953:Antigens, Protozoan; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C090009:kinetoplastid membrane protein 11, Leishmania donovani; D016753:Interleukin-10; C093139:LACK antigen, Leishmania; D007371:Interferon-gamma