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 ± 0.54×10-10M for controls versus 0.90 ± 0.55×10-10M 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 contribution of our observations to the osteolytic activity of these cytokines deserve further investigation.
