Comparison of the bone-resorbing activity in the supernatants from phytohemagglutinin-stimulated human peripheral blood mononuclear cells with that of cytokines through the use of an antiserum to interleukin 1.

We compared the bone-resorbing activity in the conditioned medium from phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cell cultures with that of partially purified human monocyte-derived interleukin 1 (IL-1), human recombinant IL-1 alpha (pI 5) and IL-1 beta (pI 7), human recombinant tumor necrosis factor-alpha (TNF alpha), and PTH in fetal rat long bone cultures. An antiserum to the products of activated human mononuclear cells, including IL-1, completely blocked the bone-resorbing activity of all three forms of IL-1 and of unfractionated PHA-stimulated human peripheral blood mononuclear cell supernatants, but did not inhibit resorption stimulated by recombinant human TNF alpha. This antiserum also had no effect on the resorptive response to 3 nM PTH, but did decrease the response to 1 nM PTH slightly. These results imply that IL-1, but not TNF alpha, mediates the bone-resorbing activity found in the supernatants of PHA-stimulated human peripheral blood mononuclear cell cultures. It is not known whether the small inhibitory effect that the antiserum to IL-1 had on the response to 1 nM PTH resulted from a nonspecific action or an effect of PTH on local IL-1 synthesis in bone. Since cytokines are found in the circulation of normal individuals and are produced at local sites of pathology, these results suggest that they can influence both normal and abnormal skeletal metabolism.