Kinetics of a Cellular Response to Interleukin 6

The stimulation of the production of haptoglobin from the human hepatoma HepG2 was used as a model to examine the kinetics of a cellular response to interleukin 6 (IL-6). It was demonstrated that IL-6 upregulated the production of haptoglobin in a time-dependent manner: using a sensitive radioimmunoassay for haptoglobin, increases were already detectable 2 hr after IL-6 treatment began. The haptoglobin level continued to rise in a linear fashion to at least 16 hr. The stimulation of haptoglobin by IL-6 was abolished in the presence of 5 μg/ml actinomycin D and was thus likely pretranslational. It was further demonstrated that the upregulation of haptoglobin continued well after the removal of IL-6 from the system. An 8-hr "pulse" of IL-6 gave rise to haptoglobin secretion which was above control levels for the following 4 days. The effects of IL-6 in vivo can therefore be predicted to be long-lived despite its own short half-life, especially since the products of IL-6 stimulation, e.g., immunoglobulin and acute-phase proteins, are themselves long-lived in the circulation.