Role of macrophage infiltration in the orbital fat of patients with Graves' ophthalmopathy

Objective: Infiltration of the retro-ocular space by inflammatory cells, accumulation of glycosaminoglycans, and the overabundance of orbital adipose tissue are characteristic findings in Graves' ophthalmopathy (GO). The cause of macrophage infiltration in the orbital adipose tissue of patients with GO remains to be elucidated. Design: Immunohistochemistry of orbital adipose tissues with anti-CD68 was used for determining macrophage infiltration pattern and cell counts. Quantitative real-time PCR was used for analysing mRNA expression. Correlation of macrophage infiltration with the duration of GO and mRNA expression were also determined. Patients: Fifteen subjects with GO who underwent orbital decompression were recruited. Six patients without thyroid history who underwent elective orbital surgery were enrolled as controls. Measurements: Histological distribution of macrophages, macrophage cell counts, CD68 and monocyte chemoattractant protein-1 (MCP-1) mRNA levels, and duration of GO. Results: We demonstrated that macrophage infiltration in orbital fat from patients with GO was higher than controls (P = 0.005). The infiltration of macrophages was located primarily around blood vessels and between mature adipocytes. Macrophage infiltration did not attenuate in GO of long duration. We also found that the expression of MCP-1 was higher in GO orbital fat than that in the orbital fat of controls (P = 0.047) and the infiltration of macrophages in adipose tissue from patients with GO was positively correlated with expression of MCP-1 mRNA (r = 0.546, P = 0.035). Conclusion: Macrophage infiltration may play an important role in the pathogenesis of GO via over-expression of MCP-1.