Comparison of local cytokine gene expression and the distribution of eosinophils and CD4-positive cell subsets in the paranasal sinus mucosa between atopic and non-atopic subjects

摘要

The role of Th2 type cytokines in the persistence of chronic rhinosinusitis, especially that induced by non-infectious inflammatory causes, has been noted. However, the original cause of sinus eosi-nophilia remains unclear and whether the presence of allergic rhinitis (AR) may be a risk factor has been an issue of debate. In the present study, we examined cytokine expression and the distribution of CD4-positive cell subsets in the paranasal sinus mucosa of patients with chronic sinusitis.A total of 133 sinusitis patients was examined. Patients were subdivided into four groups based on the presence of AR and the degree of local eosi-nophil infiltration. The expression of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-5, IL-8, IL-16, eotaxin and interferon (IFN)-y mRNA was detected by reverse transcription-polymerase chain reaction. Immunohistochemical localization of CD4-, CXCR3- and CCR4-positive cells in the same specimens was quantitatively analyzed using a laser scanning confocal microscope. The group of non-AR patients with low eosinophilia (the AR(-)Eo(-) group) only showed an increase in IFN-gamma mRNA expression. In contrast, the other three groups showed similar cytokine profiles, with high expression levels for GM-CSF, IL-5 and eotaxin mRNA. The total number of CD4~+ cells was also increased in these three groups. The density of CCR4-positive CD4~+ cells was significantly higher in groups with high eosinophilia, irrespective of the presence of AR. As a result, the CXCR3~+/CCR4~+ cell ratio in the AR(-)Eo(-) group was significantly increased compared with the other three groups. These results indicate that high expression of Th2-type cytokines concomitant with the infiltration of a predominant number of CD4~+ cells and their Th2 subsets play a role in the pathogenesis of eosinophil inflammation in sinus mucosa. In addition, the finding that some of the non-atopic patients also shared Th-2 type immune responses provides support for the concept of chronic sinusitis as a Th2-mediated disease process.