Leukotrienes Play a Role in the Control of Parasite Burden in Murine Strongyloidiasis

Abstract

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 B4 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 C4, PGE2, TNF-α, IL-3, IL-4, IFN-γ, 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.

Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

“…In agreement with the results of these studies, treatment of T. canis-infected rats with a specific LTB 4 receptor antagonist significantly reduced eosinophil chemotactic activity in bronchoalveolar fluid, suggesting that LTB 4 also contributes to the accumulation of eosinophils in the lungs (33). In another study, treatment of mice infected with the nematode S. venezuelensis with the leukotriene inhibitor MK886 significantly inhibited the recruitment of eosinophils in the bronchoalveolar space, peritoneal cavity and blood (34). To determine the in vivo relevance of mast cell-derived LTB 4 in eosinophilia, we examined the release of this mediator in rats following T. canis infection.…”

Two Cases of <i>Paragonimus Westermani</i> Infection with Pulmonary and Brain Lesions

“…It has been reported that leukotrienes (LTs) increase and can be measured during parasitic infection [4][5][6] . The involvement of LTs, particularly cysteinyl leukotrienes (CysLTs), in the pathology of bronchial asthma, has been emphasized due to their potent bronchoconstrictive effects and abilities to promote vascular permeability, and drive chemotaxis of various inflammatory cells.…”

Hyperinfection Syndrome in Strongyloidiasis

“…Several immunoglobulins, such as IgE, IgG and IgM, are essential for the elimination of the parasite (Ligas et al, 2003;Machado et al, 2005). IgE antibodies can mediate the activation of accessory cells and the recognition of parasite antigens, promoting goblet cell mucus secretion and the degranulation of mast cells that release mediators affecting parasite survival (Machado et al, 2009).…”