Early Cutaneous Leishmaniasis Patients Infected With Leishmania braziliensis Express Increased Inflammatory Responses After Antimony Therapy. (6th December 2017)

• Record Type: Journal Article
• Authors: Costa, Rúbia S; Carvalho, Lucas P; Campos, Taís M; Magalhães, Andréa S; Passos, Sara T; Schriefer, Albert; Silva, Juliana A; Lago, Ednaldo; Paixão, Camilla S; Machado, Paulo; Scott, Phillip; Carvalho, Edgar M
• Is Part Of: Journal of infectious diseases. Volume 217:Number 5(2018)
• Page Start: 840
• Page End: 850
• Publication Date: 2017-12-06
• Subjects: early cutaneous leishmaniasis -- chemokines -- cutaneous leishmaniasis -- cytokines -- Leishmania braziliensis; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix627
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : Early in L braziliensis infection, progression from a papule to an ulcer is observed despite antimony therapy. Here, we show that dysfunction in the immune modulation and enhancements of inflammatory cytokines are associated with ulcer development. Abstract: Background: Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb 5 ) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb 5 therapy, which leads to treatment failure. Methods: A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb 5 and to compare immunologic responses in ECL patients with CL and healthy subjects. Results: A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb 5 treatment. Although Sb 5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL. Conclusions: The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy.