Leukotrienes play a role in the control of parasite burden in murine strongyloidiasis.
It is clear that leukotrienes mediate inflammatory response; new aspects of leukotriene function have recently been described. In this study, we demonstrate that leukotrienes are key chemical mediators in the control of parasite burdens in mice infected with Strongyloides venezuelensis. High leukotriene levels were detected in the lungs and small intestines of Swiss mice. In infected Swiss mice treated with MK886, a leukotriene synthesis inhibitor, numbers of adult worms, and eggs/g/feces were greater than in infected-only animals. The MK886 treatment inhibited leukotriene B(4) production in the lungs and small intestines, albeit on different postinfection days. Similarly, parasite burdens and eggs/g/feces were greater in 5-lipoxygenase(-/-) mice than in wild-type animals. These observation were confirmed by histopathological study of the duodena. We subsequently observed significant lower numbers of eosinophils and mononuclear cells in the blood, peritoneal cavity fluid, and bronchoalveolar lavage fluid of Swiss mice treated with MK886. In the lung parenchyma of infected animals, MK886 significantly inhibited synthesis of IL-5 at the beginning of infection, whereas levels of IL-12 increased progressively throughout the postinfection period. However, levels of leukotriene C(4), PGE(2), TNF-alpha, IL-3, IL-4, IFN-gamma, and IL-10 were comparable between the treated and untreated groups. Nevertheless, IgE and IgG1 (but not IgG2a) synthesis was also significantly inhibited by MK886 administration. Therefore, in S. venezuelensis-infected mice, adult worm and egg burdens are leukotriene dependent. These findings indicate potential immunostimulatory strategies involving leukotriene administration, and may serve as an alert to physicians treating Strongyloides stercoralis-infected patients presenting asthma-like symptoms because use of 5-lipoxygenase inhibitors may worsen the infection.
Machado
Eleuza R
ER
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Ueta
Marlene T
MT
Lourenço
Elaine V
EV
Anibal
Fernanda F
FF
Sorgi
Carlos Artério
CA
Soares
Edson G
EG
Roque-Barreira
Maria C
MC
Medeiros
Alexandra I
AI
Faccioli
Lúcia H
LH
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency / Q000502:physiology; D016207:Cytokines / Q000032:analysis / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000187:drug effects; D007421:Intestine, Small / Q000469:parasitology / Q000473:pathology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D015289:Leukotrienes / Q000032:analysis / Q000276:immunology*; D008168:Lung / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010270:Parasite Egg Count; D051381:Rats; D017208:Rats, Wistar; D013321:Strongyloides; D013322:Strongyloidiasis / Q000276:immunology* / Q000473:pathology
D016207:Cytokines; D007074:Immunoglobulin G; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D001094:Arachidonate 5-Lipoxygenase