REGULATION OF INTERLEUKIN-6 SECRETION FROM MONONUCLEAR BLOOD-CELLS BYEXTRACELLULAR CALCIUM

Interleukin-6 (IL-6) is known to enhance osteoclast recruitment, and t hereby bone resorption, Thus, IL-6 has been proposed to mediate hyperc alcemia in multiple myeloma and the enhanced osteoclastic activity see n in postmenopausal osteoporosis, We recently reported that the calciu m concentration in plasma affects IL-6 secretion from mononuclear bloo d cells, To investigate the underlying mechanism, we have studied the effect of calcium on IL-6 formation in mononuclear blood cells ex vivo and in vitro. Thirteen healthy volunteers were given 1 g of calcium o rally after overnight fasting, Plasma levels of ionized calcium (pCa(2 +)) and serum levels of parathyroid hormone (sPTH) were measured after 2 and 4 h, with all subjects still fasting, After 2 h, pCa(2+) was in creased and sPTH decreased in all 13 persons, IL-6 secretion ex vivo f rom mononuclear blood cells drawn 4 h after calcium intake was increas ed 185% as compared with IL-6 secretion from cells drawn just before c alcium intake, In control experiments without calcium intake, there wa s no alteration in pCa(2+) and no effect on IL-6 secretion from mononu clear blood cells, In vitro studies revealed that stimulation of isola ted mononuclear blood cells with physiological concentrations of calci um dose-dependently increased IL-6 secretion with an estimated EC(50) at 1.2 mM Ca2+. No effect on the IL-6 secretion was seen following tre atment of the isolated mononuclear blood cells with PTH or calcitonin, These observations demonstrate that the plasma calcium concentration affects IL-6 secretion from mononuclear blood cells, The in vitro data indicate the involvement of a direct calcium sensing mechanism. These findings might have implications in hypercalcemia and should also be borne in mind when considering the role of cytokines in osteoporosis.