Th2 Cytokines associated with Chronic Rhinosinusitis with Polyps Down-Regulate the Antimicrobial Immune Function of Human Sinonasal Epithelial Cells

Ramanathan, Murugappan; Lee, Won Kyung; Spannhake, E. W.; Lane, Andrew P.

doi:10.2500/ajr.2008.22.3136

Cited by 104 publications

(107 citation statements)

References 31 publications

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“…It has been suggested that an ineffective local Th1-based immune response in these patients is asso ciated with increased Th2-cytokine-based activity, which contributes to a chronic infection as well as to an increased presence of eosinophils, which then lead to further polyp formation (5). It has been further proposed that the weakened Th1 response in these patients may be secondary to the down-regulation of some specific toll-like receptors involved in the innate immune response (5).…”

Section: Introductionmentioning

confidence: 99%

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Cytokine Profiles in Nasal Fluid in Patients with Nasal Polyps: A Flow Cytometric Study

Perić¹,

Vojvodić²,

Radulović³

2010

Journal of Medical Biochemistry

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Cytokine Profiles in Nasal Fluid in Patients with Nasal Polyps: A Flow Cytometric StudyBiological markers in nasal fluid provide valuable information on nasal pathophysiology. The aims of this study were to compare the cytokine profiles of nasal fluid in subjects with nasal polyps (NP) and co-morbid asthma and NP patients without asthma and to determine the role of these cytokines in the development of NP. Thirty patients with NP (15 asthmatic and 15 non asthmatic) were included in this prospective study. Nasal secretion samples were collected from nasal cavities of all 30 subjects. The levels of eleven cytokines (TNF-α, TNF-β, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IFN-γ) were measured using flow cytometry. The concentrations of Th2 cytokines IL-5, IL-6 and IL-10 were significantly higher in patients with NP and asthma compared with subjects with NP without asthma. We also found significantly higher levels of IFN-α, IL-4, IL-6 and IL-10 in allergic patients with NP and asthma compared with those without asthma. In nonallergic patients with NP and asthma, the concentrations of TNF-α, IL-5 and IL-6 were significantly higher than in nonallergic patients with NP without asthma. Our results show that the presence of Th2 cytokines, especially IL-5 and IL-6 in patients with NP and asthma is a more prominent feature than in those without asthma that relates to the increased eosinophilic inflammation. We have also found a significant influence of allergy on the cytokine profiles both in asthmatic and nonasthmatic patients.

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Section: Introductionmentioning

confidence: 99%

“…It has been further proposed that the weakened Th1 response in these patients may be secondary to the down-regulation of some specific toll-like receptors involved in the innate immune response (5).…”

Section: Introductionmentioning

confidence: 99%

Cytokine Profiles in Nasal Fluid in Patients with Nasal Polyps: A Flow Cytometric Study

Perić¹,

Vojvodić²,

Radulović³

2010

Journal of Medical Biochemistry

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“…It has been shown that Th2 cytokines downregulate toll-like receptors (TLR) expression and inhibit TLR signaling function in Th1 lymphocytes membrane. Thus, Th2 cytokines inhibit Th1 cytokines production resulting in down-regulation of antimicrobial mucosal immunity [4]. Hamilos et al [20] found significantly higher levels of IL-5 in nasal polyp tissue from asthmatic than those from nonasthmatic subjects.…”

Section: Discussionmentioning

confidence: 99%

“…The initiating factor that underlie persistent inflammation and microbial colonization in NP are not well understood. Although Th2 inflammation is a central characteristic of the disease process, what triggers the local production of Th2 cytokines and infiltration of eosinophils and lymphocytes is unknown [4]. It has been shown that Th2 cytokines downregulate toll-like receptors (TLR) expression and inhibit TLR signaling function in Th1 lymphocytes membrane.…”

Section: Discussionmentioning

confidence: 99%

“…They have the primary role in the perpetuation of chronic inflammation [2,3]. It has been suggested that an ineffective local Th1-based immune response in these patients is associated with increased Th2-cytokine-based activity, which contributes to a chronic infection as well as to an increased presence of eosinophils, which then lead to further polyp formation [4]. It has been proposed that the weakened Th1 response in these patients may be secondary to the down-regulation of some specific toll-like receptors involved in the innate immune response [4].…”

Section: Introductionmentioning

confidence: 99%

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Correlation Between Cytokine Levels in Nasal Fluid and Scored Clinical Parameters in Patients with Nasal Polyposis

Perić

Vojvodić

Radulović

et al. 2012

Indian J Otolaryngol Head Neck Surg

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The aim of this study was to compare the cytokine levels in nasal fluid in subjects with nasal polyposis (NP) and co-morbid asthma and NP patients without asthma and to correlate these levels with clinical parameters of severity of disease. Forty NP patients (20 asthmatic and 20 nonasthmatic) were enrolled. Nasal secretion samples were collected from nasal cavities of all 40 subjects. The levels of Th1 cytokines IL-2, IL-12 and IFN-c, Th2 cytokines IL-4, IL-5, IL-6, and IL-10, chemokine IL-8, and proinflammatory cytokines IL-1b, TNF-a and TNF-b were measured using flow cytometric method. Each of the 40 patients was staged clinically according to global nasal symptom score, endoscopic score, and Lund-Mackay computed tomography (CT) score. The concentrations of Th2 cytokines IL-5, IL-6 and IL-10 were significantly higher (P \ 0.01, P \ 0.01, P \ 0.05) in patients with NP and asthma compared with NP patients without asthma.Positive correlations were observed between concentration of IL-2 in nasal secretions and global nasal symptom score, endoscopic score, and Lund-Mackay score only in NP patients without asthma. We also found positive correlation between CT score and the levels of IL-8, IL-4, and IL-1b in nonasthmatic patients. Finally, our results showed a positive correlation between IL-5 levels in nasal fluid and endoscopic score only in asthmatic patients. NP in asthmatic patients have different immunological patterns compared to those without asthma. We also concluded that concentrations of cytokines measured in nasal fluid were not sensitive enough to determine the severity of disease.

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Sinonasal Epithelial Cell Response toStaphylococcus aureusBurden in Chronic Rhinosinusitis

Kohanski

Lane

2015

JAMA Otolaryngol Head Neck Surg

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Importance Chronic rhinosinusitis (CRS) is an inflammatory disorder of the nose and paranasal sinuses. Staphylococcus aureus is increasingly linked with CRS exacerbations. Little is known about how bacteria activate inflammatory pathways that contribute to CRS. Objective Here, we developed an in-vitro co-culture system to explore how infection with Staphylococcus aureus stimulates innate immune responses of sinonasal epithelial cells (SNEC). Design, Setting, and Subjects SNEC were collected from 13 patients during endoscopic sinus surgery and grown in culture at the air-liquid interface. Interventions Differentiated SNEC from control, CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) patients were infected with Staphylococcus aureus at three different concentrations for 24-hours. Main Outcomes and Measures Growth of S. aureus and viability of SNEC were measured. Expression of inflammatory markers and innate immune genes were measured by RT-PCR. Basal secretion of IL-8 was determined by ELISA. Results Cultured SNEC from CRSsNP patients demonstrated a significant increase in expression of IL-8, and TNFα at all the tested concentrations of Staphylococcus aureus. Control or CRSwNP SNEC demonstrated a significant increase in expression only at the higher inoculum of Staphylococcus aureus. Basal secretion of inflammatory markers correlated with expression changes. No significant changes in expression were observed for the Th2 inflammatory mediators tested. Conclusions and Relevance In this study, we have developed a model to study early innate-immune mediated changes in sinonasal epithelial cells co-cultured at an air-liquid interface with bacteria. We also demonstrate that bacterial burden can be detected by SNEC in the absence of adaptive immune-mediated responses. CRSsNP SNECs are more sensitive to S. aureus burden than control or CRSwNP SNEC. Future studies will further develop this infection model and explore the SNEC innate immune response to bacteria.

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Th2 Cytokines associated with Chronic Rhinosinusitis with Polyps Down-Regulate the Antimicrobial Immune Function of Human Sinonasal Epithelial Cells

Cited by 104 publications

References 31 publications

Cytokine Profiles in Nasal Fluid in Patients with Nasal Polyps: A Flow Cytometric Study

Cytokine Profiles in Nasal Fluid in Patients with Nasal Polyps: A Flow Cytometric Study

Correlation Between Cytokine Levels in Nasal Fluid and Scored Clinical Parameters in Patients with Nasal Polyposis

Sinonasal Epithelial Cell Response toStaphylococcus aureusBurden in Chronic Rhinosinusitis

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