Immunological determinants of clinical outcome in Peruvian patients with tegumentary leishmaniasis treated with pentavalent antimonials

Autor: Alexandro Llanos-Cuentas, Carlo Chizzolini, Jean-Michel Dayer, Anne Maurer-Cecchini, Marleen Boelaert, Coralie Alexandrenne, François Chappuis, Gianfranco Tulliano, Jorge Arevalo, Simonne De Doncker, Louis Loutan, Saskia Decuypere, Jean-Claude Dujardin
Rok vydání: 2009
Předmět:
Antimony
Male
T-Lymphocytes
medicine.medical_treatment
America
Latin

Macrophages/immunology
Cytokines/biosynthesis
0302 clinical medicine
Peru
Interferon gamma
Prospective Studies
Child
Leishmaniasis
Skin
ddc:616
Aged
80 and over

0303 health sciences
Interleukin-13
Treatment outcomes
Middle Aged
Protozoal diseases
Interleukin-10
3. Good health
Interleukin 10
Treatment Outcome
Infectious Diseases
Cytokine
medicine.anatomical_structure
Leishmaniasis
Cutaneous/drug therapy/immunology

Child
Preschool

Interleukin 13
Cytokines
Female
Drug therapy
Antimony/therapeutic use
medicine.drug
Adult
Skin/pathology
Adolescent
mRNA
T cell
030231 tropical medicine
Immunology
Antiprotozoal Agents
Leishmaniasis
Cutaneous

Microbiology
Young Adult
Interferon-gamma
03 medical and health sciences
Immune system
Tegumentary
Cutaneous leishmaniasis
Antiprotozoal Agents/therapeutic use
medicine
Animals
Humans
Immune response
ddc:613
Aged
030304 developmental biology
Antimonials
Tumor necrosis factor alpha
business.industry
Gene Expression Profiling
T-cells
Macrophages
Infant
T-Lymphocytes/immunology
medicine.disease
Parasitology
Human medicine
Interleukin-4
Fungal and Parasitic Infections
business
Zdroj: Infection and immunity
Infection and Immunity, Vol. 77, No 5 (2009) pp. 2022-9
ISSN: 0019-9567
DOI: 10.1128/IAI.01513-08
Popis: 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.
Databáze: OpenAIRE