IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor

Abstract

We have identified and purified a factor that inhibits the production of IL-1 beta and TNF by stimulated human mononuclear cells. The activity is produced by the T cell lines Hut-78 and Mo constitutively under serum-free conditions. Crude conditioned media have titers of up to 100 U/ml (one unit defined as the reciprocal of the dilution producing 50% inhibition). The activity resides mainly in a single size peak of 30 to 35 kDa and an isoelectric point around 8. Other cytokines in this size range that have been reported to be inhibitory for IL-1 and TNF production include TGF-beta, IL-4, and IL-6; these factors were excluded by lack of detection, neutralizing antibody, and low activity compared with our factor. Another factor with these size and charge properties is IL-10, which inhibits T cell cytokine production. By polymerase chain reaction analysis, Mo and HuT-78 lines contain IL-10 transcripts whereas JURKAT is negative; this correlates with inhibitor bioactivity from the three lines. Use of mAb specifically showed the inhibitor to be IL-10.