Autophagy is a cell housekeeping mechanism that has recently received attention in relation to its effects on the immune response. Genetic studies have identified candidate loci for
Crohn's disease susceptibility among autophagy genes, while experiments in murine macrophages from ATG16L1 deficient mice have shown that disruption of autophagy increases processing of IL-1β and
IL-18 through an
inflammasome-dependent manner. Using complementary approaches either inducing or inhibiting autophagy, we describe modulatory effects of autophagy on proinflammatory
cytokine production in human cells. Inhibition of basal autophagy in human peripheral blood mononuclear cells (PBMCs) significantly enhances IL-1β after stimulation with TLR2 or TLR4
ligands, while at the same time reducing the production of TNFα. In line with this, induction of autophagy by
starvation inhibited IL-1β production. These effects of autophagy were not exerted at the processing step, as
inflammasome activation was not influenced. In contrast, the effect of autophagy on
cytokine production was on transcription level, and possibly involving the inhibition of
p38 mitogen activated protein kinase (MAPK) phosphorylation. In conclusion, autophagy modulates the secretion of proinflammatory
cytokines in human cells through an
inflammasome-independent pathway, and this is a novel mechanism that may be targeted in inflammatory diseases.