Th-2 type cytokine receptors in allergic rhinitis and in response to topical steroids.

Abstract

Th-2 type cytokine production (Interleukin-4 [IL-4] and interleukin-5 [IL5]) 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. Randomized prospective study involving 14 ragweed-allergic subjects evenly divided between placebo and corticosteroid pretreatment. 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, major basic protein (MBP), IL-4R, IL-5R, and IFN-gammaR. 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. 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.