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.