Acute Effects of Interleukin-2 on Lung Mechanics and Airway Responsiveness in Rats

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Abstract
We studied the acute effects of interleukin-2 (IL-2), the principal lymphokine responsible for lymphocyte proliferation, on lung mechanics and airway responsiveness to methacholine (MCh) in rats. Lewis (n = 12) and Fisher 344 (n = 13) rats were anesthetized and intubated, and intravenous and intra-arterial lines were inserted. IL-2 (750,000 U/kg) was infused intravenously over 2 to 4 min into seven Lewis and seven Fisher rats, and vehicle alone was administered to five Lewis and six Fisher rats. Blood pressure, heart rate, respiratory frequency (f), tidal volume (Vt), minute ventilation ( e), and lung resistance (Rl) were measured before and every 5 min for 45 min after the infusion of IL-2. Lung compliance was measured before and 30 min after IL-2. Bronchial provocation testing with MCh was performed 45 min after the infusion of IL-2. Subsequently, the animals were exsanguinated, and the lungs were removed for histologic examination. Infused IL-2 did not alter heart rate or blood pressure. Vt, f, e, and Rl increased significantly by 15 min (p < 0.05), but they returned to baseline by 45 min. Lung compliance decreased significantly in both rat strains. IL-2 increased airway responsiveness only in Lewis rats; the concentration of MCh that caused a doubling of Rl (EC200Rl) was 0.6 mg/ml and 4.3 mg/ml (p = 0.003) in IL-2-treated and control rats, respectively. The airway responsiveness did not change significantly in Fisher rats; EC200Rl was 0.13 and 0.35 mg/ml for IL-2-treated and control rats, respectively (p = 0.09). Histologic examination showed significant separation of the epithelium from the basement membrane and bronchovascular edema in both rat strains. The release of IL-2 may contribute to the altered airway responsiveness that follows antigen presentation and activation of airway lymphocytes.