Interleukin-11 inhibits il-12 production by thp-1 cells and human blood monocytes

IL-12 is a multifunctional cytokine that plays an important role in the development of Th I and Th2 lymphocytes. Previous studies from our laboratory demonstrated that IL-11 is produced by lung stromal cells in response to a variety of respiratory viral pathogens. We hypothesized that IL-11 contributes to airways pathology via an ability to regulate macrophage IL-12 production. To test this hypothesis we used a P70 ELIS A to quantitate the IL-12 production of unstimulated cells and cells treated at 24 hr intervals with IFN-y (100 ng/ml) and S. aureus Cowan strain 1 (SAC) (1:10,000 dilution). Unstimulated cells did not produce significant amounts of IL-12, while the IFN-y plus SAC treated cells produced large quantities of this cytokine. IL-11 did not stimulate IL-12 production. It did, however, inhibit IFN-Y plus SAC-induced IL-12 production. This effect was dosedependent, peaking with doses of IL-11 between 50-100 ng/ml and remaining significant with doses as low as 1 ng/ml. It was also quite potent since cells preincubated for 8 hrs with IL-11(50 ng/ml) produced 10% as much IL-12 as cells incubated with IFN-y and SAC alone (p <0.05). Interestingly, this inhibitory effect had a distinct kinetic being prominent with IL-11 preincubation, easily appreciated when IL-11 and SAC were added simultaneously and absent when IL-11 is added 8 hrs after SAC. In all cases, it did not appear to be mediated by cell cytotoxicity and did not appear to be charge-mediated since equivalent doses of poly-L-lysine did not have a similar inhibitory effect. These studies demonstrate that IL-11 is a potent inhibitor of macrophage IL-12 production. IL-11 regulation of macrophage IL-12 production may be an important event regulating Thl-Th2 phenotype at sites of local infection and/or inflammation.