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 rats.


OBJECTIVE
The purpose of this study was to investigate whether induction of 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 subcutaneously 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 leukocyte numbers were determined after enzymatic digestion of lung tissues.


RESULTS
The early response after OVA increased from 184.2% +/- 13.5% in the animals receiving saline (n = 10) to 309% +/- 51% (baseline lung resistance) in IL-2-pretreated animals (n = 17; P <.05). The late response also increased 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 administration of IL-2 (P <.05). However, IL-2-treated animals had lower levels of biliary cys-LTs during the late response than saline-treated animals but similar levels during the early response. This difference could not be attributed to an increase in LT metabolism, which we assessed by the recovery of 3H-LTC4 instilled intratracheally in challenged or unchallenged rats. When compared 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 lymphocytes were greater in the lungs of IL-2-treated than vehicle-treated and OVA-challenged rats (P <.01), and IL-2-treated rats had a lower CD4(+)/CD8(+) ratio in the blood after challenge (P <.001).


CONCLUSIONS
In conclusion, IL-2 increases early and late responses in rats, and it induces lung inflammation. Altered airway responses are not attributable to an increase in cys-LT production.
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University and the University of Montreal Hospitals Research Center, Montreal, Quebec, Canada.
P M
PM
Renzi
L
L
Xu
X X
XX
Yang
W S
WS
Powell
J G
JG
Martin
D000818:Animals; D001646:Bile / Q000737:chemistry; D001980:Bronchi / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003545:Cysteine / Q000096:biosynthesis* / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D015289:Leukotrienes / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*
D007376:Interleukin-2; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D010047:Ovalbumin; D003545:Cysteine