Endogenous regulation of the acute inflammatory response

Abstract

The acute inflammatory response has been triggered in rat lungs by deposition of IgG immune complexes. The inflammatory reaction triggered is highly tissue damaging and requires activation of NF-κB with ensuing generation of chemokines and cytokines. Endogenous generation of IL-10 and IL-13 as well as secretory leukocyte protease inhibitor (SLPI), significantly regulates this inflammatory response. IL-10 and IL-13 attenuate NF-κB activation by interfering with breakdown of IκBα, while SLPI likewise suppresses NF-κB activation, but by interfering with breakdown of IκBβ. Antibody induced blockade of IL-10, IL-13 or SLPI enhances NF-κB activation in lung and exacerbates the lung inflammatory response and injury. These data indicate that endogenous IL-10, IL-13 and SLPI are important regulators of the inflammatory response by reducing gene activation with resultant generation of peptide mediators/cytokines and chemokines.