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


METHODS
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.
Department of Otolaryngology, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Canada.
E D
ED
Wright
P
P
Christodoulopoulos
P
P
Small
S
S
Frenkiel
Q
Q
Hamid
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D005938:Glucocorticoids; D006801:Humans; D007150:Immunohistochemistry; D015848:Interleukin-5 / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D012220:Rhinitis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D000096743:Interferon gamma Receptor
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D015848:Interleukin-5; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D000096743:Interferon gamma Receptor