ELEVATED EXPRESSION OF MESSENGER-RIBONUCLEIC-ACID ENCODING IL-13 IN THE BRONCHIAL MUCOSE OF ATOPIC AND NONATOPIC SUBJECTS WITH ASTHMA

Local secretion of cytokines by T cells within the bronchial mucosa, w ith consequent selective eosinophil influx, has been implicated in the pathogenesis of bronchial asthma, The cytokine IL-13 exhibits activit ies (selective eosinophil vascular adhesion by very late antigen-4/vas cular cell adhesion molecule-1 interaction and promotion of IgE synthe sis and ''T-H2-type'' T cell responses) that may be relevant to this p rocess, We hypothesized that, compared with conditions in control subj ects, elevated expression of messenger ribonucleic acid (mRNA) encodin g IL-13 is a feature of the bronchial mucosa of both atopic (positive skin prick test result to at least one of a range of common aeroallerg ens) and nonatopic (negative skin prick test results and serum total I gE concentrations within the normal range) subjects with asthma, With use of a semiquantitative reverse transcriptase-polymerase chain react ion technique, we measured the quantities (relative to beta-actin) of IL-13 mRNA in bronchial mucosal biopsy specimens from atopic and nonat opic subjects with asthma and atopic and nonatopic control subjects. B iopsy specimens from the subjects with asthma, whether the subjects we re atopic or nonatopic, had statistically equivalent quantities of IL- 13 mRNA relative to beta-actin, and these quantities were significantl y elevated compared with those in specimens from both the atopic and n onatopic control subjects (p less than or equal to 0.02 in each case), in which the quantities of IL-13 mRNA relative to beta-actin were als o statistically equivalent, The quantities of IL-13 mRNA reflected the numbers of EG2+ eosinophils per unit area of submucosa in the biopsy specimens as determined by immunohistochemistry, which were statistica lly equivalent in the atopic and nonatopic subjects with asthma and si gnificantly elevated as compared with those in both the atopic and non atopic control subjects without asthma (p less than or equal to 0.007 in each ease), Taking the subjects with asthma as a group, no correlat ions were observed between the quantities of IL-13 mRNA (relative to p -actin) and several measures of disease severity. These data are consi stent with the hypothesis that IL-13 plays a role in the pathogenesis of both atopic and nonatopic asthma, at least partly through promoting recruitment of eosinophils to the bronchial mucosa, although ether fa ctors mag be more important in regulating the severity of the disease.