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Inhibitory Effects of Roxithromycin on Inflammatory Media Release and the Underlying Molecular Mechanisms in Chronic Rhinosinusitis

Author: AiHongHui
Tutor: XiongYuQing
School: Nanchang University
Course: Pharmacology
Keywords: Chronic Rhinosinusitis Roxithromycin IL-8 TNF-α NF-κB
CLC: R96
Type: Master's thesis
Year: 2010
Downloads: 43
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Abstract

Objective: Chronic Rhinosinusitis (CRS) is generally acknowledged as inflammatory disease and the inflammatory reaction of CRS must be controlled by drug treatment. The second generation of 14-rings macrolide was recommended as the choice for clinical medication by international official in 2007 due to the effect of potent anti-inflammatory it possesses. However, the definite mechanism of 14-rings macrolide was still not clear so that it was not widely used as clinical treatment in China. On the basis of that Roxithromycin (ROX) had definite therapeutic effectiveness on the CRS, the study mainly focused on the difference of cellular-factor expression of IL-8 and TNF-αbefore and after the treatment. Also, the molecular mechanism of cellular factor that may be regulated via NF-κB was discussed.Methods:(1)Clinical study on anti-inflammatory of ROX :45 CRS patients were selected to administrate 150mg ROX capsules (once daily, for 12 weeks), and the efficacy score (VAS score, nasal endoscopy and CT scan score) were observed before and after treatment. Blood serum was collected before and after treatment. ELISA was applied to detect the levels of IL-8 and TNF-αin blood serum. (2) The study of mucosal tissue :Diseased mucosa from the middle turbinate and unci ate was obtained from 10 CRS patients who were selected to be treated by FESS. The Diseased mucosa was then incubated with 1640 media containing various concentrations of ROX (0、10-4、10-5、10-6mol/L)and 10%FBS (named as A,B,C and D group) for 24h at 37°C and 5 % CO2. The culture supernatant was collected for the concentration detection of IL-8 and TNF-αby ELISA. (3)Then the mucosa was collected, dehydrated, paraffin embedded so as to detect the active state of NF-κB by IHC and finally compared the relation between NF-κB and IL-8 or TNF-α.Results: (1) The results of clinical study indicated that ROX treatment can effectively inhibited the serum levels of IL-8 and TNF-αafter ROX treatment(P<0.01), which suggested ROX can regulate the immune reaction by inhibiting the section of IL-8 and TNF-α. VAS score, nasal endoscopy and CT scan score was significantly decreased (P<0.01). ROX can effectively improve the systemic and local symptoms of CRS.The patients’serum levels of TNF-αreturned to normal and there was no significant difference between ROX-treated groups and normal value in a statistic analysis(P<0.01). However, even though serum levels of IL-8 was also decreased significantly, but remained significantly higher than that of the normal value. .(2) The results of mucosal tissue determination showed that the secretion of proinflammatory cytokines of the diseased mucosa from 10 patients with various doses of ROX(10-4、10-5、10-6mol/L) was suppressed. The levels of TNF-αand IL-8 in the culture supernatant were decreased significantly after treating with ROX(P<0.01). However, there was no significant difference among the ROX treated groups. (3) A discussion of Molecular ROX anti-inflammatory mechanism: the positive rate of NF-κBp65 located in the epith epithelial cell of mucosa decreased obviously among all treated groups. Meanwhile the activated expression of each treated group showed no statistic difference (P>0.05) which suggested that ROX can inhibit the activity of NF-κB. The activated expression of NF-κB among each treated group illustrated apparent positive correlation with the concentration of IL-8、TNF-αin the supernate which demonstrated that ROX can be regulated via NF-κB. Thus the expression of inflammable factor IL-8 and TNF-αcan be influenced.Conclusions:(1)ROX can efficiently control the symptoms of CRS by suppressing the secretion of IL-8 and TNF-αvia NF-κB signaling pathway. (2)ROX can inhibit the levels of cytokine IL-8, TNF-αinhibition may by degradation the activity of NF-κB .

Inhibitory Effects of Roxithromycin on Inflammatory Media Release and the Underlying Molecular Mechanisms in Chronic Rhinosinusitis

Abstract

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