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Objectives: Th-2 type cytokine production (interleukin-4 [IL-4] and interleukin-5 [IL-5]) has been demonstrated to play a significant role in the pathophysiology of allergic rhinitis (AR), and the treatment of AR with topical corticosteroids has been shown to reduce the expression of Th-2 type cytokines in vivo. However, the contribution and expression of Th-2 type cytokine receptors in AR and their response to corticosteroid treatment remain to be clarified. Objectives of the current study are 1. To examine the expression of the cytokine IL-4 and IL-5 receptors (IL-4R and IL-5R) in a nasal allergen challenge model and to contrast this with the expression of the receptor for the Th-1 type cytokine, interferon-gamma receptor (IFN-gammaR), and 2. to examine the effects of pretreatment with topical corticosteroid before allergen challenge on the expression of these same receptors.Study Design: Randomized prospective study involving 14 ragweed-allergic subjects evenly divided between placebo and corticosteroid pretreatment.Methods: Immunocytochemistry (alkaline phosphatase-antialkaline phosphatase labeling [APAAP] technique) was used to stain nasal biopsy specimens before and after allergen challenge. Antibodies used included anti-CD3, CD4, CD8, MBP, IL-4R, IL-5R, and IFN-gammaR.Results: Following allergen challenge, we observed a significant increase in the Th-2 type cytokine receptors (IL-4R and IL-5R; P < .05), as well as a significant decrease in the expression of the Th-1 type cytokine receptor (IFN-gammaR; P < .05). Pretreatment with topical corticosteroids before nasal allergen challenge resulted in decreased expression of IL-4R (P < .05) and IL-5R (P < .05) and increased expression of IFN-gammaR (P <.05). Further, IL-4R and IL-5R expression correlated with eosinophil infiltration in the tissues.Conclusions: We have demonstrated that in AR, cytokine receptors for IL-4, IL-5, and IFN-gamma follow a similar pattern to their ligands. In addition, pretreatment with topical corticosteroids was shown to alter the cytokine receptor expression pattern from a Th-2 profile more toward a Th-1 profile. [ABSTRACT FROM AUTHOR]

Objective: To study the role of superantigen (SAg) in inducing glucocorticoid (GC) receptor beta and steroid resistance in an explant model of nasal tissue., Methods: Nasal tissue was obtained from inferior turbinates of controls and ragweed (RW)-sensitive patients. Tissue samples were incubated with SAg of staphylococcal enterotoxin B. In addition, tissue samples from RW-sensitive patients were incubated with RW allergen in the presence and absence of both SAg and dexamethasone (DEX). The expression of GC receptor beta was assessed by immunocytochemistry. The expression of interleukin (IL)-2 and IL-4 mRNA was assessed by in situ hybridization., Results: SAg induced an increase in the expression of GC receptor beta in atopic tissue and to a lesser extent in nonatopic tissue. The most significant induction of GC receptor beta was observed in response to SAg and RW in atopic tissue. Stimulation of atopic tissue with RW alone and SAg alone induced IL-4 and IL-2 mRNA, respectively. Incubation of atopic tissue with both SAg and RW induced both IL-2 and IL-4 mRNA. The increase in IL-4 mRNA expression was blunted by the addition of DEX to atopic tissue stimulated with RW alone but not to tissue stimulated by both RW and SAg., Conclusion: Our results demonstrate that SAgs induce steroid resistance in atopic nasal explant tissue by up-regulating the expression of GC receptor beta. Furthermore, we have shown that the up-regulation of GC receptor beta is a local event that is associated with the coexpression of IL-2 and IL-4 mRNA.