Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy.
Interleukin-12 (IL-12) and IL-13 are two recently characterized cytokines which play an important role in the induction of T helper cell type 1 (Th1-) and Th2-like cells, respectively. Using the technique of in situ hybridization, we have investigated the expression of these cytokines in bronchial biopsies from nine allergic asthmatics and nine normal control subjects. To determine the effect of steroid therapy on the expression of IL-12 and IL-13 in asthma, the numbers of cells expressing these cytokine mRNA before and after a 1-wk course of oral prednisone in six steroid-sensitive (SS) and five steroid-resistant (SR) moderately severe asthmatics were also examined. There was an increased number of IL-13, and a decreased number of IL-12 mRNA positive cells in asthmatic subjects compared with normal control subjects (p < 0.001). After steroid treatment, the increase in FEV1 values observed in SS asthmatics was accompanied by a significant decrease in cells expressing IL-13 mRNA (p < 0.05) and an increase in the numbers of cells expressing IL-12 mRNA (p < 0.05). In contrast, steroid therapy in SR asthmatics was not associated with significant changes in IL-12 and IL-13 mRNA expression. Thus, allergic asthma is associated with a downregulation of IL-12 mRNA expression and an upregulation of IL-13 mRNA expression. These results suggest an in vivo role for IL-12 and IL-13 in modulating allergic responses and support the notion that the clinical effects of glucocorticoids are at least partially mediated through the modulation of cytokine production.
Naseer
T
T
Meakins-Christie Laboratories, Department of Pathology, McGill University, Montreal, Quebec, Canada.
Minshall
E M
EM
Leung
D Y
DY
Laberge
S
S
Ernst
P
P
Martin
R J
RJ
Hamid
Q
Q
D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018664:Interleukin-12 / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism*; D008297:Male; D011241:Prednisone / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis*
D005938:Glucocorticoids; D018793:Interleukin-13; D012333:RNA, Messenger; D018664:Interleukin-12; D011241:Prednisone