Secretion of chemokines and other cytokines in allergen-induced nasal responses: inhibition by topical steroid treatment.

We have demonstrated the detection of proallergic cytokines in the nasal secretions after antigen challenges. Our aim was to determine the secretion kinetics of chemokines (interleukin [IL]-8, macrophage inflammatory protein-1 alpha [MIP-1 alpha], and RANTES) and other cytokines (IL-1 beta and granulocyte/macrophage colony-stimulating factor [GM-CSF] after allergen challenges and their inhibition by steroid therapy. Ten allergic patients were given either beclomethasone dipropionate (BDP) or placebo in a double-blind, randomized, crossover manner. Allergen challenges were performed after 1 wk of treatment. Nasal secretions were collected serially for 11 h after allergen challenge by a matrix method. Subjects maintained symptom scores at each time point of nasal secretion recovery. Cytokines were measured by specific enzyme-linked immunosorbent assays. The mean peak values for each cytokine and total symptom scores during the early (ER) and/or late-phase reactions (LPR) were significantly reduced during the BDP treatment period (p < 0.05). The levels of cytokine correlated (p < 0.05) with corresponding total symptom scores during ER (IL-1 beta and MIP-1 alpha) and LPR (all cytokines). Our findings document local elevations of IL-1 beta, GM-CSF, and chemokines in the nasal secretions after allergen challenges and their inhibition by steroids. We speculate that the inhibition of cytokine production and secretion in the nasal mucosa may contribute to the clinical efficacy of topical steroids.

Interleukin-1 receptor antagonist protein inhibits the synthesis of IgE and proinflammatory cytokines by allergen-stimulated mononuclear cells.

The ability of interleukin-1 (IL-1) to activate diverse cell populations supports its role as a preeminent cytokine in the pathogenesis of chronic inflammation. In this study, we investigated the role of Il-1 and IL-1 receptor antagonist protein (IRAP) in the regulation of allergen-induced synthesis of IgE and proinflammatory cytokines. The temporal expression of IL-1 beta and IRAP during 5-day allergen-activated peripheral mononuclear cell (PMNC) cultures suggested differential production of the two cytokines. To determine the influence of IRAP on IL-1-mediated cellular responses, we cultured PMNC from allergic donors with specific allergens in the presence or absence of IRAP pretreatment. Culture supernatants were assayed for IgE and cytokines using specific enzyme-linked immunosorbent assay. IRAP at concentrations 0.01, 0.1, and 1 microgram/ml decreased the allergen-stimulated IgE synthesis by 33 +/- 7%, 50 +/- 7%, and 66 +/- 5%, respectively (P < 0.05). Increasing the concentration of allergen did not affect the reduction in IgE synthesis observed in the presence of IRAP. Lipopolysaccharide-stimulated IgE synthesis was also significantly inhibited by IRAP (P < 0.05). In parallel experiments, anti-IL-1 beta monoclonal antibody showed a comparable inhibitory pattern on IgE synthesis (P < 0.05). IRAP inhibited the synthesis of interleukin-6, tumor necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor in a dose-dependent manner (P < 0.05); the mean inhibition was 31 +/- 4%, 75 +/- 5%, and 88 +/- 2%, respectively, at 1 microgram/ml of IRAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Proinflammatory cytokines in nasal secretions of allergic subjects after antigen challenge.

To study the role of cytokines in allergic late-phase reactions (LPR), we measured cytokines (interleukins [IL]-1 beta, IL-2, IL-4, IL-5, IL-6, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in nasal secretions (NS) of eight allergic subjects following antigen or saline provocation. NS were collected hourly for 10 h after challenge by a newly developed matrix method. All subjects recorded hourly symptom scores. Cytokines were measured using specific enzyme-linked immunosorbent assays (ELISA). Compared with prechallenge values, significant levels of IL-1 beta were detected in all subjects during the immediate reaction (peak, 51.0 +/- 22.4 pg/ml) and LPR (peak, 78.5 +/- 22.6 pg/ml) after antigen challenges (p < 0.01) but not saline challenges. In contrast, GM-CSF and IL-6 showed a delayed rise (peak, 26.4 +/- 1.3 pg/ml and 33.8 +/- 10.0 pg/ml, respectively) at hour 4 in the antigen-challenge period (p < 0.01 versus saline). NS from 4 donors also showed detectable IL-5 (7.6 to 155 pg/ml) during the immediate reaction and LPR after allergen challenges (versus saline, p < 0.01). The levels of cytokine correlated (p < 0.05) with corresponding total symptom scores during the immediate reaction (IL-1 beta) and LPR (IL-1 beta, GM-CSF, and IL-6). IL-2 and IL-4 were not detected in any sample. Thus, IL-1 beta, IL-5, IL-6, and GM-CSF are present in the LPR of allergic rhinitis, and their correlation with clinical responses may suggest their role in allergic inflammation.

Effect of topical corticosteroids on the recovery of histamine releasing factors in nasal washings of patients with allergic rhinitis. A double-blind, randomized, placebo-controlled study.

Nasal washings (NW) have been used by many investigators as a readily available biologic fluid for studying the mechanism of allergic reactions. These fluids have been analyzed for the presence of various mediators, including cytokines. Recently, histamine releasing factors (HRF) have been detected in the NW. The objective of this study was to investigate the effect of treatment with topical corticosteroids on the recovery of these cytokines from the NW obtained from patients with allergic rhinitis. A group of 30 patients with ragweed pollen allergy were given either beclomethasone dipropionate (BDP) or placebo for 1 wk in a double-blind randomized manner. NW were performed twice before the start of the treatment period and were repeated twice at the end of the study. HRF activity was measured in the NW. Patients maintained a daily symptom score. The activity of HRF decreased significantly (mean +/- SD, pre = 37.2 +/- 21.3% versus post = 23.8 +/- 20.1%; p less than 0.01) in the BDP group, as did the mean symptom score (5.1 +/- 1.4 versus 1.5 +/- 1.5, p less than 0.01) at the end of the treatment period. In contrast, there was no significant change in HRF recovery (32.8 +/- 25.6% versus 33.8 +/- 25.3%; p less than 0.05) or symptom score (4.8 +/- 1.8 versus 5.4 +/- 1.9; p greater than 0.05) in the placebo group. There was a significant correlation between the net changes in symptom scores and the net differences in HRF activity. We speculate that the reduction in HRF in the nasal mucosa may contribute to the clinical efficacy of topical corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)