Interleukin-2-induced increased airway responsiveness and lung Th2 cytokine expression occur after antigen challenge through the leukotriene pathway.
Previous studies have shown that the allergic late airway response (LR) is dependent on the leukotriene (LT) pathway in Brown Norway (BN) rats. In this same model, interleukin-2 (IL-2) has been shown to increase allergic airway responses without increasing LT production. This study examined the relationship between the upregulation of cellular immunity with IL-2 and the LT pathway in ovalbumin-sensitized BN rats. Airway responsiveness to LTD(4) was significantly increased in BN rats pretreated with IL-2 (20,000 U twice a day for 4.5 days). Treatment with montelukast, a cysteinyl LT(1) receptor antagonist, blocked IL-2's induced increase of the LR to ovalbumin challenge. When cytokine expression was assessed either by semiquantitative polymerase chain reaction or in situ hybridization, we found that montelukast decreased the amount of IL-4 mRNA expression in the lungs while increasing the amount of interferon-gamma mRNA expression 8 hours after challenge. These results indicate that upregulation of cellular immunity with IL-2 can increase the sensitivity of the airways to LTD(4) and that inhibition of the LT pathway will block the LR and modulate cytokine expression after antigen challenge.
Nag
Sammy
S
University of Montreal Hospital Center, Notre-Dame Hospital, Quebec, Canada.
Lamkhioued
Bouchaib
B
Renzi
Paolo M
PM
D000403:Airway Resistance / Q000187:drug effects* / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007111:Immunity, Cellular / Q000187:drug effects; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000032:analysis / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation
D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D017998:Leukotriene D4; D007371:Interferon-gamma