Systemic interleukin 10 administration inhibits brain tumor necrosis factor production in mice

Interleukin 10 is an antiinflammatory cytokine and inhibits the production of tumor necrosis factor. We have previously found that intracerebroventricular (i.c.v.) administration of recombinant human interleukin 10 inhibits brain tumor necrosis factor production induced by an i.c.v. injection of lipopolysaccharide in mice. In view of its possible pharmacological use, we have now studied whether interleukin 10 administered peripherally could inhibit brain tumor necrosis factor production. Mice were injected with recombinant human interleukin 10 (20 microg/mouse, i.v.) 10 min-24 h before lipopolysaccharide (2.5 microg, i.c.v.). Tumor necrosis factor was measured, using a bioassay, in brain homogenates 90 min after lipopolysaccharide. Recombinant human interleukin 10 administered i.v. between 10 min and 6 h before lipopolysaccharide markedly inhibited brain tumor necrosis factor production. We also measured the production of tumor necrosis factor by whole blood of these mice, and it was also markedly inhibited by recombinant human interleukin 10 treatment. In conclusion, systemic recombinant human interleukin 10 administration inhibits brain tumor necrosis factor production. suggesting its usefulness in tumor necrosis factor-mediated pathologies of the central nervous system.