IL-4 and TNF-alpha increased the secretion of eotaxin from cultured fibroblasts of nasal polyps with eosinophil infiltration.

摘要

BACKGROUND: Nasal polyposis is considered a subgroup of chronic rhinosinusitis (CRS). Eosinophils are the most common inflammatory cells in nasal polyp and the degree of the tissue eosinophilia is correlated with the probability of the recurrence of nasal polyps. However, the mechanism by which eosinophils are selectively recruited in nasal polyp remains to be clarified. In the present study, fibroblasts were isolated from nasal polyps of patients with eosinophil-rich nasal polyps (Enp) and those with non-eosinophilic nasal polyps (NEnp) and the secreted levels of eotaxin, regulated upon activation normal T expressed and presumably secreted (RANTES), and vascular cell adhesion molecule-1 (VCAM-1) from the cultured fibroblasts were determined. The levels were compared between Enp and Nenp. The role of those chemokines and adhesion molecules in the pathogenesis of nasal polyp is discussed. METHODS: Fibroblasts isolated from nasal polyps of five patients with CRS with Enp and four patients with CRS with NEnp were cultured and stimulated with 10 ng/ml of tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) for 24 hours. After stimulation, culture supernatants were collected and concentrations of eotaxin, RANTES, and VCAM-1 were quantified by Enzyme linked immunosorbent assay (ELISA). RESULTS: TNF-alpha enhanced the secretion of VCAM-1 and RANTES by fibroblasts derived from both NEnp and Enp, but did not affect the release of eotaxin. IL-4 increased the secretion of VCAM-1 and eotaxin but not that of RANTES. Furthermore, TNF-alpha and IL-4, when added together, induced a synergistic effect on the secretion of VCAM-1 and eotaxin. The effect of IL-4 and IL-4 plus TNF-alpha on eotaxin release was more marked for Enp fibroblasts compared with NEnp fibroblasts. CONCLUSIONS: The results suggest that eotaxin plays an important role in the selective recruitment of eosinophils in Enp. Nasal fibroblasts in Enp are more sensitive than those in NEnp regarding eotaxin release induced by the stimulation with IL-4 and co-stimulation with TNF-alpha and IL-4. This difference might be associated with the pathogenesis of nasal polyposis having marked accumulation of eosinophils.