Regulation of interleukin-6 secretion from mononuclear blood cells by extracellular calcium.
Interleukin-6 (IL-6) is known to enhance osteoclast recruitment, and thereby bone resorption. Thus, IL-6 has been proposed to mediate hypercalcemia in multiple myeloma and the enhanced osteoclastic activity seen in postmenopausal osteoporosis. We recently reported that the calcium concentration in plasma affects IL-6 secretion from mononuclear blood 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 orally after overnight fasting. Plasma levels of ionized calcium (pCa2+) and serum levels of parathyroid hormone (sPTH) were measured after 2 and 4 h, with all subjects still fasting. After 2 h, pCa2+ was increased and sPTH decreased in all 13 persons. IL-6 secretion ex vivo from mononuclear blood cells drawn 4 h after calcium intake was increased 185% as compared with IL-6 secretion from cells drawn just before calcium intake. In control experiments without calcium intake, there was no alteration in pCa2+ and no effect on IL-6 secretion from mononuclear blood cells. In vitro studies revealed that stimulation of isolated mononuclear blood cells with physiological concentrations of calcium dose-dependently increased IL-6 secretion with an estimated EC50 at 1.2 mM Ca2+. No effect on the IL-6 secretion was seen following treatment 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.
Bornefalk
E
E
Department of Internal Medicine, University Hospital, Uppsala, Sweden.
Ljunghall
S
S
Lindh
E
E
Bengtson
O
O
Johansson
A G
AG
Ljunggren
O
O
D000284:Administration, Oral; D002118:Calcium / Q000097:blood / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood
D015850:Interleukin-6; D010281:Parathyroid Hormone; D002118:Calcium