IL-2 enhances allergic airway responses in rats by increased inflammation but not through increased synthesis of cysteinyl leukotrienes

Background: IL-2 has been shown to increase allergic airway responses in ra ts. Objective: The purpose of this study was to investigate whether induction o f inflammation and enhancement of cysteinyl-leukotriene (cys-LT) synthesis were involved in the augmentation of airway responses caused by IL-2. Methods: Brown Norway rats received human recombinant IL-2 or saline subcut aneously twice a day from day 9 to day 14 after sensitization to ovalbumin (OVA). On day 14, rats underwent either lung lavage or were challenged with an aerosol spray of OVA, the airway responses and biliary excretion of cys -LTs were measured for a period of 8 hours after challenge, and the lung le ukocyte numbers were determined after enzymatic digestion of lung tissues. Results: The early response after OVA increased from 184.2% +/- 13.5% in th e animals receiving saline (n = 10) to 309% +/- 51% (baseline lung resistan ce) in IL-2-pretreated animals (n = 17; P < .05). The late response also in creased from 19.6 +/- 4.5 (area under the curve of baseline lung resistance vs time) in the animals receiving saline to 37 +/- 5.4 after administratio n of IL-2 (P < .05). However, IL-2-treated animals had lower levels of bili ary cys-LTs during the late response than saline-treated animals but simila r levels during the early response. This difference could not be attributed to an increase in LT metabolism, which we assessed by the recovery of H-3- LTC4 instilled intratracheally in challenged or unchallenged rats, When com pared with control animals, pretreatment with IL-2 increased all cell types retrieved from lung lavage fluid before OVA challenge (P < .05). After OVA challenge, the total cell yield from lung lavage fluid was also increased, mostly because of an increase in neutrophils (P < .05). Eosinophils and ly mphocytes were greater in the lungs of IL-2-treated than vehicle-treated an d OVA-challenged rats (P < .01), and IL-2-treated rats had a lower CD4(+)/C D8(+) ratio in the blood after challenge (P < .001). Conclusion: In conclusion, IL-2 increases early and late responses in rats, and it induces lung inflammation. Altered airway responses are not attribu table to an increase in cys-LT production.