Potential Use of Interleukin-10 Blockade as a Therapeutic Strategy in Human Cutaneous Leishmaniasis.
Interleukin-10 overproduction has been associated with worse prognosis in human cutaneous leishmaniasis, while IFN-γ-dependent responses are associated with parasite killing and host protection. Innovative strategies are needed to overcome therapeutic failure observed in endemic areas. The use of monoclonal antibody-based immunotherapy targeting IL-10 cytokine was evaluated here. Partial IL-10 blockade in Leishmania braziliensis whole soluble antigen-stimulated cells from endemic area CL patients with active or healed lesions and asymptomatic controls was evaluated. Overall decrease in IL-10, IL-4, and TNF-α production was observed in all groups of subjects. Only patients with active lesions still produced some levels of TNF-α after anti-IL-10 stimulation in association with Leishmania antigens. Moreover, this strategy showed limited modulatory effects on IFN-γ-dependent chemokine CXCL10 production. Results suggest the potential immunotherapeutic use of partial IL-10 blockade in localized cutaneous leishmaniasis.
Laboratory of Immunology, Federal University of Triângulo Mineiro, 38025-180 Uberaba, MG, Brazil ; Human Immunology Research and Education Group-GEPIH, Technical Health School, Federal University of Paraíba, 58051-900 João Pessoa, PB, Brazil.
Lucio Roberto
LR
Castellano
Laboratory of Parasitology Mycology, INSERM U399, Faculty of Medicine, 27 boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
Laurent
L
Argiro
Laboratory of Parasitology Mycology, INSERM U399, Faculty of Medicine, 27 boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
Helia
H
Dessein
Laboratory of Parasitology Mycology, INSERM U399, Faculty of Medicine, 27 boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
Alain
A
Dessein
Laboratory of Immunology, Federal University of Triângulo Mineiro, 38025-180 Uberaba, MG, Brazil.
Marcos Vinícius
MV
da Silva
Infectious Diseases Division, Federal University of Triângulo Mineiro, 38025-180 Uberaba, MG, Brazil.
Dalmo
D
Correia
Laboratory of Immunology, Federal University of Triângulo Mineiro, 38025-180 Uberaba, MG, Brazil.
Virmondes
V
Rodrigues
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018925:Chemokines; D016207:Cytokines; D016753:Interleukin-10