Effect of leptin on allergic airway responses in mice

Epidemiologic data indicate that the incidence of asthma is increased in obese patients. Because the serum levels of the satiety hormone and proinflammatory cytokine leptin are increased in obese individuals, we sought to determine whether leptin can augment allergic airway responses. We sensitized and challenged BALB/cJ mice with ovalbumin. Alzet® micro-osmotic pumps were implanted in the mice to deliver a continuous infusion of either saline or leptin (1.75 μg/g/d). Two days later, the mice were challenged with either aerosolized saline or ovalbumin once per day for 3 days. We measured airway responsiveness, performed bronchoalveolar lavage, and obtained blood to measure serum leptin and IgE 24 or 48 hours after the last challenge. Leptin infusion increased serum leptin concentrations, which were increased further after ovalbumin sensitization and challenge. Ovalbumin challenge increased bronchoalveolar lavage fluid cells and cytokines, serum IgE, lung cytokine mRNA expression, and responses to inhaled, aerosolized methacholine. It is important to note that the changes in methacholine responsiveness and IgE were augmented in leptin- versus saline-infused mice. These results indicate that serum leptin is increased during allergic reactions in the airways and may play a role in the relationship between obesity and asthma.