Regulation of lymphocyte calcitonin receptors by interleukin-1 and interleukin-6.
We have reported the existence of specific and high-affinity calcitonin (CT) receptors on normal human T-lymphocytes. Because of the increasingly recognized importance of interleukin-1 (IL-1) and IL-6 in the control of bone metabolism, we have examined their influence on the binding parameters of labeled salmon calcitonin (sCT) on lymphocytes. After a 24-hour incubation, IL-1 at 100-5000 U/ml and IL-6, at 1-1000 U/ml, decreased the apparent number of CT binding sites (Bmax) on T-lymphocytes. The effects of IL-6 on purified T-lymphocytes were dose related and 100 U of IL-6/ml reduced sCT binding to 57 +/- 16% (mean +/- SD) of the control values (n = 6). There was no significant change in CT binding affinity (Kd, 0.71 +/- 0.54 x 10(-10) M for controls versus 0.90 +/- 0.55 x 10(-10) M after IL-6) and the decrease in Bmax was reversible after 48 hours. The effects of IL-1 appeared to be mediated through an increased production of IL-6 as they were neutralized by a polyclonal antiserum against IL-6. Added alone, the antiserum caused a slight increase in the apparent number of CT binding sites on T-lymphocytes to 115 +/- 5% of control values (n = 3). In summary, IL-1 and IL-6 can induce a marked apparent loss of CT binding sites on normal T-lymphocytes at concentrations known to be active on bone metabolism. The contributions of our observations to the osteolytic activity of these cytokines deserve further investigation.
Bone Metabolism Unit, Institut J. Bordet, Université Libre de Bruxelles, Belgium.
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D000818:Animals; D001862:Bone Resorption / Q000209:etiology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002116:Calcitonin / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D018003:Receptors, Calcitonin / Q000187:drug effects* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D000093242:Interleukin-6 Inhibitors
D002116:Calcitonin; D007375:Interleukin-1; D015850:Interleukin-6; D018003:Receptors, Calcitonin; D000093242:Interleukin-6 Inhibitors; C028815:salmon calcitonin