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.
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Bone Metabolism Unit, Institut J. Bordet, Université Libre de Bruxelles, Belgium.
Fernandez
G
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Lacroix
M
M
Vandenbussche
P
P
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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