Changes of serum cytokines in hyperthyroid Graves' disease patients at diagnosis and during methimazole treatment.
OBJECTIVE
Cytokines are involved in the pathogenesis of Graves' disease (GD), but ambiguous serum cytokine results have been described.


METHODS
We studied the changes in serum interleukin (IL)-1β, soluble IL-2 receptor (sIL-2R), IL-5, IL-6 and tumor necrosis factor (TNF)-α concentrations in 29 untreated GD patients before and after restoration of euthyroidism with methimazole (MMI) treatment compared to 25 control subjects. Eleven out of 29 GD patients had active Graves' ophthalmopathy (GO).


RESULTS
Compared to controls, untreated GD patients had significantly higher median levels of serum IL-1β (18.7 vs. 34.0 pg/ml), sIL-2R (292.5 vs. 1,585.0 pg/ml), IL-5 (1.0 vs. 9.0 pg/ml), IL-6 (3.0 vs. 5.0 pg/ml) and TNF-α (8.1 vs. 16.0 pg/ml). In euthyroidism following MMI treatment, concentrations of IL-1β (25.0 pg/ml), sIL-2R (362.0 pg/ml), IL-5 (3.0 pg/ml), IL-6 (3.0 pg/ml) and TNF-α (5.0 pg/ml) declined significantly and were similar to controls. The greatest reductions were noted in sIL-2R (76.9%), TNF-α (68.8%) and IL-5 (66.6%) levels. Serum sIL-2R, IL-5 and TNF-α levels in active GO patients were significantly elevated, but no significant differences were observed in GD patients without GO. Using a multiple linear regression analysis, serum IL-1β was significantly associated with free thyroxine, sIL-2R with triiodothyronine and serum thyrotropin receptor antibody (TRAb) and TNF-α with TRAb.


CONCLUSIONS
These results support the notion that serum cytokines could be used as a marker of GD activity, and the decrease in cytokine levels might be related to the achievement of euthyroidism and the immunomodulatory effects of MMI treatment.
Pedro
Ana Beatriz B
AB
Endocrinology, Hospital Servidor Publico Estado de São Paulo-IAMSPE, São Paulo, Brazil.
Romaldini
João H
JH
Takei
Kyoko
K
D000293:Adolescent; D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood*; D005260:Female; D006111:Graves Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D049970:Graves Ophthalmopathy / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D008875:Middle Aged; D013960:Thyroid Function Tests; D055815:Young Adult
D013956:Antithyroid Agents; D016207:Cytokines; D008713:Methimazole