Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase

Interleukin-10 (IL-10) inhibited the production of superoxide anion (O₂^-) by both unactivated and interferon-γ (IFN-γ)-activated human monocytes. Simultaneous addition of IL-10 with IFN-γ at the start of incubation was necessary for an optimal inhibitory effect. The degree of inhibition was substantially comparable to that of IL-4, and the combination of suboptimal concentrations of IL-10 and IL-4 produced 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 heavy chain subunit of cytochrome b₅₅₈ (gp91-phox) and 47-kD cytosolic factor (p47-phox), components of the O₂^--generating NADPH oxidase system. Reduction of the mRNAs was distinct within 24 hours. On the other hand, the induced O₂^- production by human monocytic leukemia cell lines (THP-1 and HL60) was not inhibited by IL-10. The amount of gp91-phox and p47-phox mRNAs remained unchanged even in the presence of excess amount of IL-10. Taken together, these results suggest that IL-10 inhibits O₂^- production by downregulation of the gp91-phox and p47-phox genes in human monocytes.