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 micrograms/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.
Peppard
J V
JV
Research Department, Ciba-Geigy Corporation, New Jersey 07901.
Smith
H D
HD
Zhou
S
S
D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006242:Haptoglobins / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D006242:Haptoglobins; D015850:Interleukin-6; D003609:Dactinomycin