Lymphokine-induced airway hyperresponsiveness in the rat.
We evaluated the potential role of the lymphocyte in chronic airway inflammation and responsiveness by repeated administration to rats of interleukin-2 (IL-2), the principal lymphokine responsible for lymphocyte proliferation. Lewis rats (mean weight, 184 +/- 2 g) received either 120,000 units of IL-2 (n = 10) or vehicle (n = 7) subcutaneously twice a day for 4.5 days. Animals were anesthetized with urethane and intubated for measurements of pulmonary resistance (RL) and airway responsiveness to aerosol methacholine (MCh). Lung lavage was performed, the animals were exsanguinated, and the lungs were fixed in 10% formalin. Histologic edema and the extent of infiltration of the bronchi, pulmonary veins, and arteries by cells was scored blindly. IL-2 increased airway responsiveness to MCh; the concentrations of MCh causing a doubling of RL were 0.14 versus 1.39 mg/ml (geometric mean) for the IL-2 and vehicle group, respectively (p = 0.001). IL-2 significantly increased total cellular return and the percentage of lymphocytes, neutrophils, and eosinophils in lavage. IL-2 caused edema and a mixed cellular infiltration of the bronchovascular tree. Lymphocytes predominated around the airways and veins. A correlation (r = 0.50) was present between airway responsiveness and airway inflammation but not with edema or vascular infiltration. Release of IL-2 by lymphocytes in the airways may be an important mediator of airway hyperresponsiveness.
Renzi
P M
PM
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Sapienza
S
S
Du
T
T
Wang
N S
NS
Martin
J G
JG
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D007376:Interleukin-2 / Q000494:pharmacology*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology; D011654:Pulmonary Edema / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D015656:Respiratory Mechanics; D007507:Therapeutic Irrigation
D007376:Interleukin-2; D016210:Methacholine Chloride