ATP INDUCES THE RELEASE OF IL-1 FROM LPS-PRIMED CELLS IN-VIVO

The secretion of IL-1 from murine macrophages in vitro is an inefficie nt process that is distinct from those of other cytokines such as IL-6 . We have therefore studied this process in vivo to see if these diffe rences are maintained. Intraperitoneal injection of LPS in mice induce d production and release of IL-6 into the extracellular fluid (periton eal lavage). Although induction of intracellular IL-1 alpha and IL-1 b eta was readily detected, these cytokines were not detected extracellu larly. Injection of ATP 2 h after LPS led to the rapid extracellular r elease of IL-1 beta, IL-1 alpha, lactate dehydrogenase, and beta-N-ace tylglucosaminidase. Western blot analysis revealed that a large propor tion of the IL-1 beta was released as the 17-kDa form, whereas IL-1 al pha was unprocessed. Adenosine 5'-O-(3-thiotriphosphate) was also effe ctive in causing IL-1 release but not UTP or ADP. This suggests that t he ATP-mediated release of IL-1 is a receptor-mediated phenomenon that is associated with cell lysis.