Interleukin-13 and -4 induce death of activated microglia

When the brain suffers injury, microglia migrate to the damaged sites and become activated. These activated microglia are not detected several days later and the mechanisms underlying their disappearance are not well characterized. In this study, we demonstrate that interleukin (IL)-13, an anti-inflammatory cytokine, selectively induces cell death of activated microglia in vitro. Cell death was detected 4 days after the coaddition of IL-13 with any one of the microglial activators, lipopolysaccharide (LPS), ganglioside, or thrombin. This cell death occurred in a time-dependent manner. LPS, ganglioside, thrombin, or IL-13 alone did not induce cell death. Among anti-inflammatory cytokines, IL-4 mimicked the effect of IL-13, while TGF-β did not. Cells treated with IL-13 plus LPS, or IL-13 plus ganglioside, showed the characteristics of apoptosis when analyzed by electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Electron micrographs also showed microglia engulfing neighboring dead cells. We propose that IL-13 and IL-4 induce death of activated microglia, and that this process is important for prevention of chronic inflammation that can cause tissue damage.