SUPPRESSION OF SUPEROXIDE ANION PRODUCTION BY INTERLEUKIN-10 IS ACCOMPANIED BY A DOWN-REGULATION OF THE GENES FOR SUBUNIT PROTEINS OF NADPHOXIDASE

Interleukin-10 (IL-10) inhibited the production of superoxide anion (O -2(-)) by both unactivated and interferon-gamma (IFN-gamma)-activated human monocytes. Simultaneous addition of IL-10 with IFN-gamma at the start of incubation was necessary for an optimal inhibitory effect. Th e degree of inhibition was substantially comparable to that of IL-4, a nd the combination of suboptimal concentrations of IL-10 and IL-4 prod uced an additive effect. A similar effect was also obtained when viral IL-10 (vIL-10) was used instead of IL-10. The inhibitory effect of IL -10 was accompanied by the reduced accumulation of transcripts for hea vy chain subunit of cytochrome b(558) (gp91-phox) and 47-kD cytosolic factor (p47-phox), components of the O-2(-)-generating NADPH oxidase s ystem. Reduction of the mRNAs was distinct within 24 hours. On the oth er hand, the induced O-2(-) production by human monocytic leukemia cel l lines (THP-1 and HL60) was not inhibited by IL-10. The amount of gp9 1-phox and p47-phox mRNAs remained unchanged even in the presence of e xcess amount of IL-10. Taken together, these results suggest that IL-1 0 inhibits O-2- production by downregulation of the gp91-phox and p47- phox genes in human monocytes.