A_2A receptors are critical for IL-10 production by E coli–challenged macrophages. (A) E coli and adenosine synergize in inducing IL-10 production by A_2A receptor WT peritoneal macrophages. E coli both in the absence and presence of adenosine fails to induce IL-10 production by A_2A KO macrophages. A_2A KO and WT peritoneal macrophages were treated with heat-killed E coli (at a macrophage:bacterium ratio of 1:15) or cotreated with 100 μM adenosine and heat-killed E coli for 5 hours, and then IL-10 was measured from the supernatant using enzyme-linked immunosorbent assay. ***P < .001 vs. E coli A_2A WT group. (B) Effect of adenosine receptor agonists on IL-10 production. The agonists were added to macrophages before stimulating with E coli. IL-10 concentrations were measured from the supernatants taken 5 hours after E coli stimulation. ***P < .001 vs. vehicle. (C) E coli and adenosine synergize in inducing IL-10 production by A_2B receptor WT and, to a lesser extent, A_2B KO peritoneal macrophages. A_2B KO and WT peritoneal macrophages were treated with heat-killed E coli or cotreated with 100 μM adenosine and heat-killed E coli for 5 hours, and then IL-10 was measured from the supernatant using enzyme-linked immunosorbent assay. **P < .01 vs. E coli A_2B WT group. Results (mean ± SEM) shown are representative of at least 3 experiments with n = 6 in each experiment.