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Furthermore, smoking may suppress development of tolerance toward thyroid autoantigens.[] Smoking may also create a proinflammatory environment, where immune responses are exacerbated due to reduced inhibition of IL-1 receptor antagonist (IL-1Ra) on IL-1 stimulation,[] although some authors do report no effect of cigarette smoking on serum IL-1/IL-1Ra concentrations in patients of thyroid-associated orbitopathy.[] Though cigarette smoke have been found to enhances adipogenesis in cultured human orbital fibroblasts, clinical studies generally find smoking associated with an increase in muscle volume rather than fat volume in GO.[] Cigarette smoke also alters the chemical composition of tear in patients with GO,[] but the clinical significance of this finding is currently unknown

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