Systemic expression of inflammatory mediators in patients with chronic rhinosinusitis and nasal polyps with and without Aspirin Exacerbated Respiratory Disease

Systemic expression of inflammatory mediators in patients with chronic rhinosinusitis and nasal polyps with and without Aspirin Exacerbated Respiratory Disease

Author Pezato, Rogerio Autor UNIFESP Google Scholar
Swierczynska-Krepa, Monika Google Scholar
Niankowska-Mogilnicka, Ewa Google Scholar
Holtappels, Gabriele Google Scholar
De Ruyck, Natalie Google Scholar
Sanak, Marek Google Scholar
Derycke, Lara Google Scholar
Van Crombruggen, Koen Google Scholar
Bachert, Claus Google Scholar
Perez-Novo, Claudina A. Google Scholar
Abstract Background: Systemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD. Methods: Patients with nasal polyposis and asthma with AERD (n = 20) and without (n = 18) were orally challenged with aspirin in a single-blind placebo controlled study. Serum samples and urine were collected before and 6 h after placebo and aspirin oral challenges. Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA. The concentrations of 9-alpha, 11-beta prostaglandin F-2, and leukotriene E-4 (uLTE(4)) were measured in urine samples by ELISA. The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges. Results: AERD patients showed significantly higher baseline levels of s-IL-5R-alpha, uLTE(4) and percentage of CD4(+)CD25(+)CD127(pos) and CD4(+)CD45RA(-)CD45RO(+) but decreased levels of TGF-beta(1) and number of CD4(+)CD25(+)CD127(neg) cells. Aspirin challenge induced the release of uLTE4, IL-6 and increased the number of CD4(+)CD45RA(-)CD45RO(+) memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects. Further, IL-8 and sIL-5R-alpha levels directly correlated with the PD(20)ASA and the effects of aspirin on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction (bronchial and nasal). Conclusions: AERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease. Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients. (C) 2015 Elsevier Ltd. All rights reserved.
Keywords Aspirin Exacerbated Respiratory Disease
Interleukin 6
Memory T-cells
Oral aspirin challenge
Systemic reaction after aspirin challenge
Interleukin 8
IL-5 receptor alpha
TGF-beta(1)Sensitive Patients
Bronchial-Asthma
T-Cells
Moderate Asthma
Hypersensitivity
Challenge
Activation
Tgf-Beta-1
Association
Leukocytes
Language English
Sponsor Flemish Research Board (FWO) [FWO08-PDO-117]
Flemish Scientific Research Board (FWO) [A12/5-HB-KH3, 1841713N, G039412N]
Interuniversity Attraction Poles (IAP) Project [P7/30]
Jagiellonian University [K/ZDS/000362]
Grant number This work was supported by a grant to Dr. Claudina Perez-Novo from the Flemish Research Board (FWO Post-doctoral mandate, Nr. FWO08-PDO-117), grants to Prof. Claus Bachert from the Flemish Scientific Research Board (FWO Nr. A12/5-HB-KH3, FWO mandate: 1841713N and FWO research project: G039412N), the Interuniversity Attraction Poles (IAP) Project P7/30 and the statutory grant from the Jagiellonian University (K/ZDS/000362) awarded to Dr. Monika Swierczynska-Krepa.
Date 2016
Published in Cytokine. London, v. 77, p. 157-167, 2016.
ISSN 1043-4666 (Sherpa/Romeo, impact factor)
Publisher Academic Press Ltd- Elsevier Science Ltd
Extent 157-167
Origin http://dx.doi.org/10.1016/j.cyto.2015.10.011
Access rights Closed access
Type Article
Web of Science ID WOS:000366540500020
URI http://repositorio.unifesp.br/handle/11600/49703

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