Efficacy of histamine H1 receptor antagonists azelastine and fexofenadine against cutaneous Leishmania major infection.

Autor: Peniche AG; Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America., Osorio EY; Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America., Melby PC; Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.; Center for Tropical Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America., Travi BL; Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States of America.; Center for Tropical Diseases, University of Texas Medical Branch, Galveston, Texas, United States of America.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2020 Aug 10; Vol. 14 (8), pp. e0008482. Date of Electronic Publication: 2020 Aug 10 (Print Publication: 2020).
DOI: 10.1371/journal.pntd.0008482
Abstrakt: Current drug therapies for cutaneous leishmaniasis are often difficult to administer and treatment failure is an increasingly common occurrence. The efficacy of anti-leishmanial therapy relies on a combination of anti-parasite activity of drugs and the patient's immune response. Previous studies have reported in vitro antimicrobial activity of histamine 1-receptor antagonists (H1RAs) against different pathogens. We used an ex vivo explant culture of lymph nodes from mice infected with Leishmania major to screen H1RAs compounds. Azelastine (AZ) and Fexofenadine (FX) showed remarkable ex vivo efficacy (EC50 = 0.05 and 1.50 μM respectively) and low in vitro cytotoxicity yielding a high therapeutic index. AZ significantly decreased the expression of H1R and the proinflammatory cytokine IL-1ẞ in the ex vivo system, which were shown to be augmented by histamine addition. The anti-leishmanial efficacy of AZ was enhanced in the presence of T cells from infected mice suggesting an immune-modulatory mechanism of parasite suppression. L. major infected BALB/c mice treated per os with FX or intralesionally with AZ showed a significant reduction of lesion size (FX = 69%; AZ = 52%). Furthermore, there was significant parasite suppression in the lesion (FX = 82%; AZ = 87%) and lymph nodes (FX = 81%; AZ = 36%) with no observable side effects. AZ and FX and potentially other H1RAs are good candidates for assessing efficacy in larger studies as monotherapies or in combination with current anti-leishmanial drugs to treat cutaneous leishmaniasis.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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