Serum soluble interleukin 2 (IL-2) receptor (sIL-2R) in differentiated thyroid carcinoma

Abstract

Increased concentrations of serum soluble interleukin-2 (IL-2) receptor (sIL-2R), a marker of T-lymphocyte activation, have been found in several metastatic solid tumors. To our knowledge, no information is available on serum sIL-2R in differentiated thyroid carcinoma (DTC). Aim of this study was to evaluate whether disease activity and/or thyroid status may affect circulating sIL-2R in DTC, since it is has recently been demonstrated that serum thyroid hormone concentration positively modulates circulating sIL-2R. DTC patients were divided into 3 groups: Group A: 48 patients without metastases or local recurrences; Group B: 16 patients with cervical lymph node metastases; Group C: 22 patients with distant metastases. All patients were evaluated after total thyroidectomy both off and on L-thyroxine (L-T4) therapy. Control group was composed by 20 healthy euthyroid subjects. sIL-2R was assayed by solid-phase ELISA. In the hypothyroid state, sIL-2R levels of Group A were significantly lower when compared to normal controls (256±130 vs. 461±186 U/ml, p<0.001 by Student t test); Group B and Group C patients off L-T4 therapy had sIL-2R concentrations significantly higher (479±407 U/ml, Group B; 519±746 U/ml, Group C) when compared to hypothyroid patients of Group A (p<0.01 and p<0.05, respectively), but not significantly different from normal euthyroid controls. Administration of L-T4 was associated in Group A with a significant increase up to normal levels of serum sIL-2R (568±295, p<0.0001 vs. the untreated state) as well as in Group B (728±437, p<0.05 vs. the untreated state). In Group C, SIL-2R concentrations (630±432 U/ml) observed during L-T4 treatment were not significantly different from those observed in the hypothyroid status. When all patients were individually examined, serum sIL-2R increased after L-T4 therapy in 79 out of 86 cases (91%) and decreased in the remaining 7 (9%) cases. Decrease of serum sIL-2R levels on L-T4 was significantly associated (x²: 30.4, p<0.0001) to high (>910 U/ml) serum sIL-2R concentration off L-T4 therapy. No significant correlation between serum sIL-2R and serum thyroglobulin was observed both in hypothyroid (r=0.12, p=0.3) and in euthyroid (r=0.09, p=0.3) patients. No significant correlation was found between circulating sIL-2R and tumor histotype, duration of disease, previous amount of administered radioiodine and presence of antithyroid autoantibodies. In conclusion, the present study suggests that thyroid status and disease progression modulate serum sIL-2R. In patients free of disease, circulating sIL-2R appear to be strictly dependent on the thyroid status. In contrast, high serum sIL-2R was observed in some patients with metastatic DTC off L-T4 therapy, in spite of the hypothyroid state. This phenomenon is unrelated to several parameters of disease progression and its clinical meaning is unclear.