Kyosuke Furukido

Nuclear Factor-Kappa B Activation in the Nasal Polyp Epithelium: Relationship to Local Cytokine Gene Expression†

Objectives A panel of cytokines has been found to be important for eosinophil accumulation and activation in nasal polyps. The aims of this study were to ascertain whether the activation of nuclear factor‐kappa B (NF‐κB) occurred in the polyp epithelium, and to examine the relationship between the degree of activation and local cytokine gene expression.

Leukotriene Receptor Antagonist Pranlukast Suppresses Eosinophil Infiltration and Cytokine Production in Human Nasal Mucosa of Perennial Allergic Rhinitis

The purpose of this study was to investigate the influence of pranlukast on eosinophilic inflammation and cytokine production in human nasal mucosa. Twelve patients were treated with pranlukast, and samples were obtained from the nasal mucosa of the inferior turbinate. With respect to cell infiltration, a significant decrease was observed in the percentage of inflammatory cells (secreted eosinophil cationic protein [EG2] and neutrophil elastase) after treatment. The levels of cytokines and chemical mediators (interleukin [IL]–4, IL-5, RANTES [regulated on activation, normal T cell expressed and secreted], cysteinyl leukotrienes, IL-1β, tumor necrosis factor–α, and IL-8) assessed by enzyme-linked immunosorbent assay and enzyme immunoassay were significantly decreased. These results indicate that pranlukast decreased the levels of a majority of the cytokines in nasal mucosa, leading to improvement in subjective nasal symptoms. Furthermore, these results support the hypothesis that pranlukast exerts its therapeutic action primarily by blocking the leukotriene receptors on eosinophils.

Suppression of the Th2 pathway by suplatast tosilate in patients with perennial nasal allergies.

Background Suplatast tosilate (IPD-1151T), a selective Th2 cytokine inhibitor that suppresses the production of interleukin (IL)-4 and IL-5 in vitro or in animal models has been proved clinically effective for allergic rhinitis (AR). The aim of this study was to investigate changes in the Th2 pathway in human nasal mucosa after medication with IPD-1151T. Twelve patients were treated with IPD-1151T. Methods Twelve healthy volunteers served as normal controls. The following parameters were evaluated: (i) subjective nasal clinical symptoms, (ii) percentages of inflammatory cells (EG2, CD4, and CD8) by immunocytological staining, and (iii) levels of cytokines (IL-4, IL-5, IL-13, regulated on activation, normal T-cell expressed, and secreted [RANTES], and interferon [IFN] γ) by enzyme-linked immunosorbent assay. Results Nasal symptom scores significantly decreased after treatment. With respect to cell infiltration, a significant decrease was observed in the percentage of inflammatory cells (EG2 and CD4) and CD4/CD8 ratio. The levels of cytokines (IL-4, IL-5, IL-13, and IFN-γ) and the IL-5/IFN-γ ratio were significantly decreased, and the IL-4/IFN-γ ratio became not significantly different from that in normal subjects. In contrast, RANTES did not change significantly. The percentage of reduction in IL-5 correlated with that in eosinophil infiltration, whereas that in RANTES did not. Conclusion These results suggest that IPD-1151T can reduce the Th2 pathway.

Analysis of local cytokine gene expression in patients with allergic rhinitis treated with CO2 laser surgery.

Objectives/Hypothesis Laser surgery of the inferior turbinates has become a popular surgical treatment for patients with allergic rhinitis, particularly for those who have persistent nasal obstruction and do not respond well to pharmacological therapy. The aim of this study was to investigate the effects of the laser surgery on local cytokine gene expression at the mucosal surface in relation to the improvement of nasal symptoms.

Study of eosinophil activation in nasal mucosa in patients with perennial nasal allergy: effects of CO2 laser surgery.

Carbon dioxide (CO2) laser surgery has been shown to be clinically effective in the treatment of nasal allergy. To investigate the mechanisms of eosinophil infiltration and activation underlying the therapeutic effects of CO2 laser surgery, we examined changes in the cytological profile of nasal mucosa after surgery. Twenty-two patients with perennial nasal allergy against house-dust mites underwent two or three rounds of laser surgery at 1-month intervals on an outpatient basis. The following parameters were evaluated at each visit: (i) improvement of clinical symptoms (nasal obstruction, rhinorrhea, and sneezing), (ii) percentage of infiltrating eosinophils in nasal mucosa, and (iii) the degree of EG2+ cells and intracellular adhesion molecule 1 (ICAM-1) expression by immunocyto-chemistry. All clinical symptoms significantly decreased after surgery. Significant reductions in eosinophil infiltration (p < 0.01) and the percentage of EG2+ cells (p < .005) were observed also. However, the degree of ICAM-1 expression in epithelial cells was not changed. These results suggest that CO2 laser surgery partially reduced the allergic reactions, leading to improvement of clinical symptoms.

Influence of Inflammatory Cells in Paranasal Mucosa on Cultured Human Sinus Ciliated Cells. The Influence of Eosinophil Infiltration.

Although recently there have been an increasing number of reports of chronic sinusitis acompanied with a high level of eosinophils, there is little evidence that eosinophils influence epithelial cells in the paranasal sinus. In this study, we focused on the difference in infiltration cells, especially eosinophil infiltration, on the ciliary beat frequency (CBF) of cultured human sinus epithelial cells. Sinus mucosal explants were successfully cultured on poly-L-lysine coated dishes with an abundant outgrowth of ciliated cells. CBF measurement was carried out by photoelectric method at specific predetermined sites on 7 to 10 day cultured specimens. In this study, CBF in eosinophil infiltration (more than 51 cells/ 100 pmt) was significantly higher (p < 0.05) than CBF in eosinophil infiltration (less than 50 cells/100 pm2). On the other hand, CBF was not significantly different among the groups of mononuclear cell infiltration (more than 51 cells/100 pmt and less than 50 cells/100 pm2). Moreover, CBF in less than 0.3 (eosinophils/mononuclear cells) was significantly higher (p <0.05) than CBF in more than 0.3 (eosinophils/mononuclear cells). Thus we suggest that eosinophil infiltration in human sinus mucosa is influenced by the level of CBF.