Thyroid hormone regulation of cell migration and oxidative metabolism in polymorphonuclear leukocytes: Clinical evidence in thyroidectomized subjects on thyroxine replacement therapy

Migration and superoxide anion (O-2(-)) generation were studied in polymorphonuclear leukocytes (PMNs) from 14 athyreotic patients, previously treated by total thyroidectomy and radioiodine therapy for differentiated thyroid carcinoma, and from age- and sex-matched euthyroid healthy controls. Patients were studied twice: in hypothyroidism (visit 1) and after TSH-suppressive L-T-4 replacement therapy (visit 2). Random migration and N-formyl-Met-Leu-Phe (fMLP) 0.1-mu M induced chemotaxis were similar in cells from patients at both visit I and visit 2 and from healthy controls. On the contrary, resting O-2(-) generation in cells from patients was significantly lower than control values, both at visit 1 and 2. At visit 1, fMLP 0.1 mu M-induced O-2(-) generation was significantly lower than control values, while phorbol-myristate acetate (PMA) 100-ng/ml induced O-2(-) generation was similar in cells from patients and from controls. At visit 2 both responses increased, resulting in fmLP-induced O-2(-) generation superimposable to control values and PMA-incluced O-2(-) generation significantly higher with respect to both visit 1 and cells from controls. In vitro exposure of PMNs from healthy subjects to L-T-4 did not affect O-2(-) generation in resting cells, and significantly increased that induced by fMLP or PMA only at high, supra-physiological concentrations. Neither TSH nor T-3 had significant effects at any of the concentrations tested. The present results document the existence of a correlation between thyroid status and oxidative metabolism of human PMNs, which is however unlikely to depend upon a direct action of thyroid hormones on these cells. (c) 2005 Elsevier Inc. All rights reserved.