Interleukin 1 interacts synergistically with forskolin and isobutylmethylxanthine in stimulating bone resorption in organ culture.

This study examined the interaction of interleukin 1 (IL-1) with forskolin and isobutyl-methylxanthine (3-isobutyl-1-methyl-xanthine) (IBMX) in stimulating bone resorption in 5-day fetal rat long bone organ culture. Forskolin and IBMX are pharmacologic agents that elevate cyclic adenosine monophosphate (AMP) levels in many cell types, including osteoblasts and osteoclasts. The interaction of IL-1 with forskolin and IBMX are synergistic when submaximal resorptive concentrations of agonists were examined. Stimulated resorption was 2 to 5 times that expected for an additive response. When maximally resorptive concentrations of agonists were examined, the interaction between IL-1 and the other agents was, at most, additive. We have previously reported that parathyroid hormone and prostaglandin E, agents that also activate the cyclic AMP pathway in bone cells, interact synergistically with IL-1 in stimulating bone resorption. The results of this study, together with our previous studies, suggest that activation of the cyclic AMP pathway is a sufficient signal for an agent to interact synergistically with IL-1 in stimulating bone resorption.