Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy.

Abstract

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.

Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair

“…IL-13 seems to be necessary for collagens I, III, and V because they show little induction in its absence. Interestingly, IL-13 has been implicated in the pathogenesis of asthma in a number of studies, and increased deposition of collagens I, III, and V has been observed in the lungs of asthmatic patients (51)(52)(53)(54). Thus, IL-13 stimulates the precise collagens responsible for the pulmonary fibrosis seen in asthma patients.…”

Endogenous IL-12 synthesis is not required to prevent hyperexpression of type 2 cytokine and antibody responses

“…Individuals with atopic dermatitis [13,14], asthma [15,16] or allergic rhinitis [16,17], the most common form of atopy, are reported to exhibit substantially reduced IL-12 synthesis and/or responsiveness relative to non-atopic controls, a finding consistent with a potential role for such defects in the pathogenesis of allergic disease. In vivo studies in mice using anti-IL-12 Ab or with strains genetically deficient in Fig.…”

Exacerbation of Experimental Allergic Asthma by Augmented Th2 Responses in WSX-1-Deficient Mice

“…IL-5 promotes differentiation and migration of eosinophils (7)(8)(9). IL-13 is highly expressed in Th2 cells from asthma patients (10) and plays a role in the development of allergic asthma (11,12) by acting on epithelial cells to produce AHR and mucus production (13). These results indicate that inappropriate development of Th2 responses plays a central role in the development of asthma.…”