Deficiency in interleukin-10 production by M2 macrophages in eosinophilic chronic rhinosinusitis with nasal polyps

M2 macrophages are characterized by high interleukin-10 (IL-10) expression and are critical for resolving inflammation. Although increased accumulation of M2 macrophages has been demonstrated in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly the eosinophilic type, their functional relevance in CRSwNP remains poorly understood.

M1 and M2 macrophages and IL-10 expression in sinonasal tissues were detected by double-immunofluorescence staining. THP-1 cells, a human monocytic leukemia cell line, were stimulated with various cytokines to study macrophage polarization and IL-10 expression. Polyp size, computed tomography (CT) scans, and symptom severity were scored.

Compared with numbers in control tissues, the numbers of total CD68⁺ macrophages, interferon regulatory factor 5-positive and CD68⁺ M1 macrophages, and CD163⁺ CD68⁺ and CD206⁺ CD68⁺ M2 macrophages were increased in both eosinophilic and non-eosinophilic polyps. However, compared with non-eosinophilic polyps, eosinophilic polyps contained fewer M1 macrophages and more M2 macrophages. Consistent with this, the M1/M2 macrophage ratio was increased in non-eosinophilic polyps, whereas it decreased in eosinophilic polyps. Strikingly, the numbers of IL-10⁺ CD68⁺ macrophages and the percentage of IL-10⁺ CD68⁺ macrophages relative to the total number of macrophages were decreased in eosinophilic polyps, despite the upregulation of M2 macrophages in this type of polyp. The number of IL-10⁺ CD68⁺ M2 macrophages correlated negatively with total symptoms scores, polyp sizes, total CT scores, and the total number of inflammatory cells in patients with eosinophilic CRSwNP. Poly I:C downregulated IL-10 expression in M2 macrophages differentiated from THP-1 cells in vitro.

Impaired IL-10 production by M2 macrophages may contribute to sustained inflammation in eosinophilic CRSwNP.vv.