Superantigen-Induced Glucocorticoid Insensitivity in the Recurrence of Chronic Rhinosinusitis with Nasal Polyps

2011 ◽  
Vol 145 (5) ◽  
pp. 717-722 ◽  
Author(s):  
Mingming Wang ◽  
Peng Shi ◽  
Bei Chen ◽  
Guanggang Shi ◽  
Hong Li ◽  
...  

Objective. To investigate a potential mechanism by which superantigens could induce glucocorticoid insensitivity in chronic rhinosinusitis (CRS) patients. Study Design. Prospective cohort study. Setting. Tertiary medical center. Subjects and Methods. Sinonasal polyps were obtained from CRS patients with nasal polyps (CRSwNP; 20 without recurrence, 18 with recurrent NP followed for 1.5-2.0 years) and nasal mucosa from 16 CRS patients without nasal polyps (CRSsNP). Specimens were tested by enzyme-linked immunosorbent assay for staphylococcal exotoxins (SEs) including SEA, SEB, SEC, SED, and toxic shock syndrome toxin type-1 (TSST-1) and assessed by immunohistochemistry for glucocorticoid receptor (GR) α and β, and the GRβ/GRα ratio was analyzed. Results. In CRSwNP, 13 of 18 (72.22%) subjects with subsequently recurrent NP, 11 of 20 (55.00%) subjects without NP recurrence, and 1 of 16 (6.25%) CRSsNP subjects with positive reactions for SEs were obtained. There were no positive results in controls. The expressions of GRβ in 3 CRS groups and controls were significantly different (all P < .05), and a similar increasing tendency of the GRβ/GRα ratio was found among groups besides the comparison of CRSwNP versus recurrent NP groups ( P = .053). Furthermore, there was a clear trend of increased GRβ expression in the enzyme-linked immunosorbent assay (ELISA)–positive samples compared with ELISA-negative samples. Concerning GRα, the expression was enhanced significantly just in toxin-positive recurrent NP versus controls ( P = .048), but the relative induction of GRβ was much higher, thereby leading to a higher GRβ/GRα ratio. Conclusions. Bacterial superantigens may contribute to glucocorticoid insensitivity through induction of GRβ, which appears to be a marker of steroid insensitivity in CRSwNP.

OTO Open ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 2473974X1987507
Author(s):  
Ashley Lonergan ◽  
Theoharis Theoharides ◽  
Eirini Tsilioni ◽  
Elie Rebeiz

This pilot study was undertaken to isolate and quantify substance P (SP) and hemokinin 1 (HK-1) in the nasal lavage fluid of patients with chronic rhinosinusitis with nasal polyps to better elucidate the pathophysiology underlying this inflammatory process, which remains poorly understood. Mucus samples were collected from this introductory cohort of 10 patients diagnosed with chronic rhinosinusitis with nasal polyps at Tufts Medical Center (Boston, Massachusetts). Relative levels of SP and HK-1 were measured with enzyme-linked immunosorbent assay methods. Both inflammatory neuropeptides were found in detectable and comparable amounts in patient samples and in concentrations up to 100-fold those established in past literature. The presence of SP and HK-1 necessitates further investigation into their role in nasal polyposis and the potentiation of the chronic inflammation inherent to chronic rhinosinusitis. Downregulating these peptides could therefore provide novel treatment targets to manage this disease process.


Author(s):  
Wagner Vargas Souza Lino ◽  
André Luis Lacerda Bachi ◽  
José Arruda Mendes Neto ◽  
Gabriel Caetani ◽  
Jônatas Bussador do Amaral ◽  
...  

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.


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