Leukotriene B4-loaded microspheres as a new approach to enhance antimicrobial responses in Histoplasma capsulatum-infected mice.
Histoplasmosis is a pulmonary disease characterised by chronic granulomatous and suppurative inflammatory reactions caused by Histoplasma capsulatum. Regarding new therapies to control fungal infections, the aim of this study was to investigate whether pulmonary administration of leukotriene B(4) (LTB(4))-loaded microspheres (MS) could confer protection to 5-lipoxygenase knockout (5-LO(-/-)) mice infected by H. capsulatum. In this study, MS containing LTB(4) were administered intranasally to mice infected by H. capsulatum. On Day 14 after the infection, fungal recovery from the lungs and histology were evaluated and inflammatory cytokines were measured. Pulmonary administration of LTB(4)-loaded MS was able to reduce fungal recovery from infected lungs. Production of important inflammatory cytokines related to host defence was augmented following MS administration to the lungs. Lung histology also showed that infected mice presented a clear reduction in the fungal burden following the pulmonary release of LTB(4) from MS. Our study provides evidence that the proposed biodegradable microparticulate system, which can release LTB(4) to the lungs, can be employed as therapy, enhancing the antimicrobial activity of host cells during histoplasmosis.
Nicolete
Roberto
R
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil.
Secatto
Adriana
A
Pereira
Priscilla A T
PA
Soares
Edson G
EG
Faccioli
Lúcia H
LH
D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006016:Glycolates; D006658:Histoplasma / Q000187:drug effects*; D006660:Histoplasmosis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D019344:Lactic Acid; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D008084:Lipoxygenase / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008172:Lung Diseases, Fungal / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016896:Treatment Outcome
D016207:Cytokines; D006016:Glycolates; D007975:Leukotriene B4; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008084:Lipoxygenase