Effects of endogenous glucocorticoid deprivation on immune response of allergic rhinitis in mice

Abstract

Objective: To study the effect of dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis on the pathogenesis of allergic rhinitis (AR) by the mouse model of decreased endogenous glucocorticoid (GC) after adrenalectomy, and further explore the mechanism of neural-endocrine regulation. Methods: According to literatures, adrenalectomized (ADX) mice and AR model were established. Eighty mice were randomly divided into four groups (n=20 per group) including control group, AR group of normal mice (AR group), AR group of bilateral ADX (bilateral ADX/AR group) and AR group of unilateral ADX (unilateral ADX/AR group). In order to assess the model of ADX, adrenal gland tissue was assayed by HE staining and the plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The behavioral observation, OVA-sIgE assessments and count of eosinophils/mast cells by the HE/Toluidine Blue staining of nasal septum mucosa tissue were performed to evaluate the AR model. The expression of peripheral blood CD4(+) IL4(+) T cells (Th2 cells) and CD4(+) IFN-γ(+) T cells (Th1 cells), splenocytes of CD4(+) CD25(+) Treg cells (Treg cells) were measured by flow cytometry to study the influence of endogenous GC on immunological indexes in different groups of mice. SPSS 16.0 software was used to analyze the data. Results: The concentrations of OVA-sIgE in control group, AR group, bilateral ADX/AR group and unilateral ADX/AR group mice were (28.86±3.62) ng/ml, (76.27±16.47) ng/ml, (48.37±8.89) ng/ml, (49.86±7.19) ng/ml, respectively. There was statistically significant difference between control group and AR group (t=7.09, P<0.05), AR group and bilateral ADX/AR group (t=4.81, P<0.05), AR group and unilateral ADX/AR group (t=5.21, P<0.05). The level of Th2 cells in different four groups were (0.71±0.24)%, (7.03±1.95)%, (2.44±2.06)%, (3.20±1.21)%, respectively. There was statistically significant difference between control group and AR group (t=-2.93, P<0.05), AR group and bilateral ADX/AR group (t=-4.67, P<0.05), AR group and unilateral ADX/AR group (t=-3.61, P<0.05). The expression of Th2 in bilateral ADX/AR group is lower than that in unilateral ADX/AR group without significant difference (t=4.39, P>0.05). Meanwhile, the level of Th1 cells in different four groups was (0.58±0.76)%, (0.57±0.59)%, (0.72±0.34)%, (1.03±0.32)%, respectively, with no significant difference among these groups. The proportion of Treg cells was (11.10±2.18)%, (4.10±1.07)%, (7.15±0.92)%, (4.58±1.05)%, respectively, with significant difference between control and other groups (t value was -7.171, -8.273, -8.360, respectively, all P<0.05). Compared with AR group, Treg cells increased significantly in bilateral ADX/AR group (t=-2.607, P<0.05). In addition, lower expression of eosinophil and mast cell were detected in the local nasal tissue of bilateral ADX/AR group, and mast cell degranulation wasn't be observed. Conclusion: Unilateral or bilateral ADX leads to HPA axis dysfunction and endogenous GC deprivation, possibly regulating the mechanism of AR through Th1/Th2 immune bias and Tregs cell' activity.