Cytokine profiles in eye muscle tissue and orbital fat tissue from patients with thyroid-associated ophthalmopathy

Eye muscle (EM) and retroorbital fat tissue are two major sites of involvem ent in thyroid-associated ophthalmopathy (TAO). Lymphocytic infiltration in these tissues is a prominent histological feature of TAO. We have investig ated the cytokine gene profiles in EM and orbital fat (OF) tissues from pat ients with TAO. Total RNA was isolated from EM tissue of 14 patients and fr om OF tissues of 29 patients with TAO, Cytokine gene expression was assesse d by RT-PCR using paired primers for interferon gamma (IFN gamma), tumor ne crosis factor alpha (TNF alpha), interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-10, CD4, CD8, and glyceraldehyde-3-phosphate dehydrogenase. IFN gamma, TNF alpha, IL-1 beta, and IL-6 messenger RNA (mRNA) were mainly detected in EM tissue, whereas IL-4 and IL-10 mRNA were detected in only one patient. On the other hand, in OF tissue, IL-4 and IL-10 mRNA were detected in 24% a nd 38% of the patients, respectively, and IFN gamma IL-1 beta, and IL-6 mRN A were less often detected compared with EM tissue. The enlargement of EM t issue as assessed by computed tomography correlated significantly with TNF alpha mRNA expression in EM tissue. The orbital volume was positively corre lated with IL-6 mRNA expression and negatively correlated with IL-4 mRNA an d IL-10 mRNA expression in OF tissue. These results suggest that T helper ( Th) 1-like cytokines predominate in EM tissue in most patients and that the predominant cytokine profile in OF tissue varies from patient to patient. Both Th1-like and Th2-like immune responses may play roles in the developme nt of two components of ophthalmopathy.