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 inefficient 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 differences are maintained. Intraperitoneal injection of LPS in mice induced production and release of IL-6 into the extracellular fluid (peritoneal lavage). Although induction of intracellular IL-1 alpha and IL-1 beta was readily detected, these cytokines were not detected extracellularly. Injection of ATP 2 h after LPS led to the rapid extracellular release of IL-1 beta, IL-1 alpha, lactate dehydrogenase, and beta-N-acetylglucosaminidase. Western blot analysis revealed that a large proportion of the IL-1 beta was released as the 17-kDa form, whereas IL-1 alpha was unprocessed. Adenosine 5'-O-(3-thiotriphosphate) was also effective in causing IL-1 release but not UTP or ADP. This suggests that the ATP-mediated release of IL-1 is a receptor-mediated phenomenon that is associated with cell lysis.