Interferon gamma mRNA “superinduction” in human lymphocytes

Human peripheral blood mononuclear lymphocytes produce interferon gamma (IFN-γ) in response to stimulation by mitogens. Previous studies on the kinetics of IFN-γ mRNA production upon mitogen induction, showed that steady-state levels of mRNA increased to a maximum at 12–24h post-induction after which they declined to levels not detectable by the assay used. We show here that in mitogen induced peripheral blood lymphocytes, inhibition of protein synthesis using three different inhibitors (cycloheximide, puromycin, pactamycin) resulted in an increase in the steady-state levels of IFN-γ mRNA. The levels of mRNA in cells treated with inhibitor 16h post-induction were up to 3-fold higher than in untreated cells. Superinduction was possible up to 40h post-induction after which the steady-state levels of mRNA had declined to limits below detection; IFN-γ mRNA was not superinduced by cycloheximide in the presence of actinomycin D.