title: Immunological determinants of clinical outcome in Peruvian patients with tegumentary leishmaniasis treated with pentavalent antimonials.
abstract: The mechanisms linking the immune response to cutaneous and mucosal leishmaniasis (CL and ML, respectively) lesions and the response to treatment are incompletely understood. Our aims were to prospectively assess, by quantitative reverse transcription-PCR, the levels of mRNA for gamma interferon, tumor necrosis factor alpha, interleukin-10 (IL-10), IL-4, and IL-13, as well as the presence of T cells (CD2) and macrophages (CD68), in CL and ML lesions and to follow their changes in response to treatment with pentavalent antimonials. The leishmanin skin test (LST) was performed on all CL and ML patients before treatment. The patient population included individuals living in areas of Peru where the disease is endemic, i.e., 129 with CL and 43 with ML. Compared to CL patients, the LST induration size was larger, the levels of all cytokine mRNAs but IL-10 were higher, T-cell mRNA was similar, and macrophage mRNA was lower in ML patients. The proportion of CL patients with an LST induration size of >8 mm was higher among responders to treatment. In CL, the pretreatment levels of cytokine mRNAs did not discriminate between responders and nonresponders; however, treatment was more often accompanied by a reduction in the levels of T-cell and cytokine mRNAs in responders than in nonresponders. Furthermore, the production of cytokines per T cell and macrophage decreased with treatment but IL-10 production remained high in nonresponders. Overall, these findings point to complex relationships among New World Leishmania parasites, skin and mucosal immune responses, and treatment outcome. The persistence of high levels of IL-10 in CL is characteristically associated with a poor response to treatment.
authors.affiliation: Immunology & Allergy, Geneva University Hospital, 1211 Geneva 14, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Maurer-Cecchini
authors.forename: Saskia
authors.initials: S
authors.lastname: Decuypere
authors.forename: François
authors.initials: F
authors.lastname: Chappuis
authors.forename: Coralie
authors.initials: C
authors.lastname: Alexandrenne
authors.forename: Simonne
authors.initials: S
authors.lastname: De Doncker
authors.forename: Marleen
authors.initials: M
authors.lastname: Boelaert
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
authors.forename: Louis
authors.initials: L
authors.lastname: Loutan
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dayer
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Tulliano
authors.forename: Jorge
authors.initials: J
authors.lastname: Arevalo
authors.forename: Alexandro
authors.initials: A
authors.lastname: Llanos-Cuentas
authors.forename: Carlo
authors.initials: C
authors.lastname: Chizzolini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000965:Antimony / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010568:Peru; D011446:Prospective Studies; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; D016207:Cytokines; D000965:Antimony