Both Th1- and Th2-derived cytokines in serum are elevated in Graves' ophthalmopathy

Abstract

Increased serum cytokine levels have been reported in patients with autoimmune thyroid disease, but less is known about their levels in patients with Graves' ophthalmopathy (GO). It is not known whether GO is a cell‐mediated or humoral autoimmune disease. We investigated whether serum cytokines are elevated in GO patients and whether the cytokines were Th1‐ or Th2‐derived. In addition, elevated cytokines might reflect the activity of GO, and thus we investigated whether cytokine levels could predict the clinical response to orbital radiotherapy. We studied 62 consecutive patients with moderately severe untreated GO and 62 healthy controls, matched for sex, age and smoking habits. Serum concentrations of IL‐1RA, sIL‐2R, IL‐6, sIL‐6R, tumour necrosis factor‐alpha (TNF‐α) RI and II and sCD30 were measured using highly sensitive ELISAs, in the patients before and 3 and 6 months after radiotherapy. All patients were euthyroid, with anti‐thyroid drugs, before and during the entire study period. All baseline cytokine and cytokine receptor levels were significantly elevated in GO patients compared with healthy controls, except for IL‐1RA. The levels did not correlate with parameters of the thyroid disease, nor with the duration, activity or severity of GO. However, backward logistic regression analysis showed that IL‐6, sCD30 and TNFαRI were able to predict a beneficial response to orbital radiotherapy. We therefore conclude that both Th1‐ and Th2‐derived cytokines are elevated in GO patients compared with its controls. IL‐6, sCD30 and TNFαRI had some value for predicting therapeutic outcome to orbital irradiation, and may thus reflect active eye disease.

IL-1β Induces IL-6 Expression in Human Orbital Fibroblasts: Identification of an Anatomic-Site Specific Phenotypic Attribute Relevant to Thyroid-Associated Ophthalmopathy

“…Wahrenberg et al (24) have reported that adipose tissues from these individuals release several-fold higher levels of IL-6 than do similar tissues from control subjects. Circulating IL-6 levels have also been found to be elevated in Graves' disease (17)(18)(19)(20)(21)(22). Moreover, treatment of thyrotoxicosis fails to normalize these levels, suggesting strongly that they are a consequence of the underlying autoimmune process.…”

Role of Chemokines in Endocrine Autoimmune Diseases

“…A major difference between active and inactive GO is the presence of a lymphocytic infiltrate in orbital tissues (161,162). Thus, the increased production of CXCL10 might be sustained by orbital lymphocytes.…”

Th1 and Th2 Serum Cytokine Profiles Characterize Patients with Hashimoto’s Thyroiditis (Th1) and Graves’ Disease (Th2)

“…In addition, 210 Neuroimmunomodulation 2004;11:209-213 Phenekos/Vryonidou/Gritzapis/Baxevanis/ Goula/Papamichail cytokines potentiate the expression of both major histocompatibility complex class I and II molecules by thyroid follicular cells and upregulate expression of adhesion and complement regulatory molecules [11][12][13][14]. Cytokines have also been implicated in the pathogenesis of thyroidassociated ophthalmopathy by inducing fibroblast proliferation and increased production of glycosaminoglycans, resulting in eye muscle and orbital tissue fat enlargement [15][16][17][18].…”