Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice

Background: Epidemiologic data indicate an increased incidence of asthma in the obese. Objective: Because serum levels of the insulin-sensitizing and anti-inflammatory adipokine adiponectin are reduced in obese individuals, we sought to determine whether exogenous adiponectin can attenuate allergic airway responses. Methods: We sensitized and challenged BALB/cJ mice with ovalbumin (OVA). Alzet micro-osmotic pumps were implanted in the mice to deliver continuous infusions of buffer or adiponectin (1.0 μg/g/d), which resulted in an approximate 60% increase in serum adiponectin levels. Two days later, mice were challenged with aerosolized saline or OVA once per day for 3 days. Mice were examined 24 hours after the last challenge. Results: OVA challenge increased airway responsiveness to intravenous methacholine, bronchoalveolar lavage fluid cells, and T _H2 cytokine levels. Importantly, each of these responses to OVA was reduced in adiponectin- versus buffer-treated mice. OVA challenge caused a 30% reduction in serum adiponectin levels and a corresponding decrease in adipose tissue adiponectin mRNA expression. OVA challenge also decreased pulmonary mRNA expression of each of 3 proposed adiponectin-binding proteins, adiponectin receptor 1, adiponectin receptor 2, and T-cadherin. Conclusion: Our results indicate that serum adiponectin is reduced during pulmonary allergic reactions and that adiponectin attenuates allergic airway inflammation and airway hyperresponsiveness in mice. Clinical implications: The data suggest that adiponectin might play a role in the relationship between obesity and asthma.