INTERLEUKIN-10 DECREASES 92-KD GELATINASE ACTIVITY FROM ACTIVATED PORCINE ALVEOLAR MACROPHAGES. • 251

Abstract

Alveolar macrophages (AMs) secrete several matrix metalloproteinases (MMP), including the 92 kd type IV collagenase-gelatinase, which may play a role in lung injury. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has been shown to decrease 92 kd gelatinase and PGE2 from concanavalin-A stimulated human monocytes [Mertz, et al, J. Biol. Chem. 269:21322, 1994]. To determine the effect of IL-10 on AM 92 kd gelatinase and PGE2, lungs from pigs 2-4 wks of age were lavaged with phosphate buffered saline and AMs were cultured in RPMI 1640 (2 × 106 cells/ml). AMs were pretreated with recombinant human IL-10 (0, 5 and 20 ng/ml) × 30 min followed by stimulation with lipopolysaccharide [LPS (1u g/mL)] or phorbol myristate acetate [PMA (5 ug/ml)]. Conditioned media was collected after 48 hrs of incubation. Gelatinase activity was measured by zymogram SDS-PAGE activity gels and PGE2 was measured by RIA. rhIL-10 at both doses completely attenuated the LPS induced increase in gelatinase activity and partially attenuated the increase seen with PMA. Interestingly, rhIL-10 slightly increased 92-kd gelatinase activity from unstimulated AMs. rhIL-10 had no effect on the increase in PGE2 seen with both LPS and PMA. These results suggest that IL-10 decreases alveolar macrophage 92kd gelatinase in a PGE2 independent fashion. Furthermore, IL-10 may decrease matrix degradation in LPS mediated lung injury.