Effect of LACK and KMP11 on IFN‐γ Production by Peripheral Blood Mononuclear Cells from Cutaneous and Mucosal Leishmaniasis Patients

• Published in: Scandinavian journal of immunology Vol. 61; no. 4; pp. 337 - 342
• Main Authors: Carvalho, L. P., Passos, S., Dutra, W. O., Soto, M., Alonso, C., Gollob, K. J., Carvalho, E. M., Ribeiro de Jesus, A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK; Malden, USA Blackwell Science Ltd 01-04-2005
• Subjects: Adolescent; Adult; Animals; Antigens, Protozoan - immunology; Antigens, Protozoan - pharmacology; Child; Down-Regulation - drug effects; Down-Regulation - immunology; Humans; Hypersensitivity, Immediate - drug therapy; Hypersensitivity, Immediate - immunology; Immunophenotyping; Interferon-gamma - biosynthesis; Interferon-gamma - blood; Interferon-gamma - immunology; Interleukin-10 - biosynthesis; Interleukin-10 - blood; Interleukin-10 - secretion; Leishmania; Leishmania braziliensis - immunology; Leishmaniasis, Cutaneous - blood; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - parasitology; Leishmaniasis, Visceral - blood; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - parasitology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - parasitology; Male; Membrane Glycoproteins - immunology; Membrane Glycoproteins - pharmacology; Middle Aged; Protozoan Proteins - immunology; Protozoan Proteins - pharmacology; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/j.1365-3083.2005.01581.x

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‐γ (IFN‐γ) 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‐γ 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‐γ levels by 52% in CL patients and by 19% in ML patients. Addition of LACK to SLA‐stimulated cultures decreased IFN‐γ 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‐γ response, even inducing IL‐10 production.