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INTRODUCTION
Cytokines are soluble polypeptides released from cells of the immune system. Their production in endocrine glands and their actions on hormone-responsive cells is currently a subject of intense research interest. There is strong evidence for the involvement of cytokines in the pathogenesis of autoimmune diabetes and thyroid disease. In addition they may regulate the growth and differentiated function of cells as they are known to do in the reticuloendothelial system. Cytokines may thus contribute to the development of functional endocrine disturbances and neoplasms. They are also involved in bone modelling processes and their action may be disturbed in disorders of bone. Greater understanding of the effects of cytokines will give insight into normal regulatory processes in endocrine tissues and may lead to therapeutic advances. The aim of this article is to review these actions and to speculate as to their physiological and pathophysiological significance as well as
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Abstract
Elevation of non-esterified fatty acids (NEFA) in vivo is associated with abnormal control of TSH. To determine whether TSH secretion is directly inhibited by NEFA, as has been reported for GH, cultured rat anterior pituitary cells were exposed for 20 h to oleic acid in medium containing 77 × 10−5 mol/l bovine serum albumin (BSA). In a molar ratio with albumin of 1·2 (total oleic acid 9× 10 mol/l), or greater, oleic acid inhibited basal GH secretion (maximum inhibition to 40% of control) while basal TSH was less affected, a ratio of 3 (2·3 × 10−4 mol/l oleic acid) or greater causing a smaller degree of inhibition (maximum inhibition to 80% of control). In the presence of 10−9 mol/l growth hormone-releasing hormone or 108 mol/l TRH, inhibition was achieved at a ratio of 12 (9 × 10−4 mol/l oleic acid) or greater. Basal TSH was less sensitive to inhibition by thyroxine (T4) in the presence of oleic acid/albumin at a ratio of 6 or greater, and inhibition by oleic acid was less than additive with T4 at a ratio of 6 or greater. Responses to tri-iodothyronine (T3) were unaffected at a ratio of 6 (4·6 × 10−4 mol/l oleic acid), but a ratio of 12 inhibited the effects of both T3 and T4 on TSH. Oleic acid had less effect in the presence of TRH, a ratio of 12 causing a small increase in the threshold concentration of T3 and T4 for TSH inhibition. Further studies are required to determine the mechanism by which oleic acid inhibits the response of basal TSH to T4 as well as the reason for a reduced effect of oleic acid in the presence of TRH. In some critically ill patients, total serum NEFA/albumin ratios from 1·5 to 6 have been reported, indicating that the direct inhibitory effects on TSH observed in vitro occur at free NEFA concentrations achieved in vivo. However, the direct inhibitory effect on TSH may be offset to some extent by reduced responsiveness to T4 at higher oleic acid concentrations. Hence other sites of action of NEFA in vivo may also be important in limiting TSH secretion. Further studies should examine the hypothalamic hormones like TRH and somatostatin, which control the thyrotrophs, as potential sites of action of NEFA.
Journal of Endocrinology (1994) 143, 557–564
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ABSTRACT
Interleukin-6 (IL-6) has actions on a variety of endocrine tissues. The cytokine is secreted by cells of the anterior pituitary and endocrine pancreas and has recently been shown to be produced by cultures of thyroid epithelial cells. In this study we have examined some of the factors which regulate IL-6 release from an immortalized human thyroid line (HTori3).
IL-6 release over 24 h was stimulated by TSH (5000 μU/ml), by forskolin (0·01 mmol/l), by fetal calf serum (1–20%) and by epidermal growth factor (20 ng/ml). Stimulation was also apparent with γ-interferon and with tumour necrosis factor at concentrations known to enhance class II major histocompatibility antigen expression by thyroid epithelium. The most potent factor tested was interleukin-1 (IL-1), which controls IL-6 release from other cell types. Threefold stimulation was found with 1 U/ml rising to 350-fold with 1000 U/ml. The effect of IL-1 took 2 h to develop and was blocked by cycloheximide (100 μmol/l). Stimulation was not markedly inhibited by pertussis toxin. Many of the actions of IL-1 are mediated by prostaglandin E2 (PGE2). At concentrations as low as 30 nmol/l, PGE2 stimulated IL-6 release but the maximum stimulation obtained with PGE2 was only threefold. The effect of IL-1 was not inhibited by indomethacin.
These data provide further evidence that IL-6 is produced by human thyrocytes. The effect of IL-1 has not been demonstrated previously. Stimulation of IL-6 release by IL-1 did not appear to be mediated by prostaglandin. IL-6 may influence hormone release from the thyroid as it does in other tissues. High concentrations of IL-6 in the thyroid may increase infiltration by, and activation of, lymphocytes in patients with autoimmune thyroid disease.
Journal of Endocrinology (1992) 133, 477–482
