Altered cytokine export and apoptosis in mice deficient in interleukin-1Beta converting enzyme

The interleukin-1 β (IL-1β converting enzyme (ICE) processes the inactive IL-1 P precursor to the proinflammatory cytokine. Adherent monocytes from mice harboring a disrupted ICE gene ([ICE.sup.-/-] did not export IL-1β or interleukin-1α (IL-1α) after stimulation with lipopolysaccharide. Export of tumor necrosis factor-α and interleukin-6 (IL-6) from these cells was also diminished. Thymocytes from [ICE.sup.-/-] mice were sensitive to apoptosis induced by dexamethasone or ionizing radiation, but were resistant to apoptosis induced by Fas antibody, Despite this defect in apoptosis, [ICE.sup.-/-] mice proceed normally through development.
The cytokine IL-1β plays a pivotal role in acute and chronic inflammation, bone resorption, myelogenous leukemia, and other pathological processes (1). IL-1β is synthesized as a 31-kD precursor devoid of [...]