Inhibition by Glucocorticosteroid Hormones of Interferon and Prostaglandin E Induction by Poly(rI).Poly(rC)

Abstract

SUMMARYWe have examined the relationship between induction of interferon (IFN) and prostaglandin E (PGE) production by poly(rI), poly(rC) in cultured human foreskin fibroblasts (FSll). Hydrocortisone and dexamethasone (2.5 x 10 -7 M), which are known inhibitors of PGE synthesis, significantly decreased the induction of both IFN and PGE in IFN-pretreated (primed) cells. Desoxycorticosterone, progesterone and estradiol were devoid of this activity. Hydrocortisone also blocked the induction of IFN by double-stranded RNA (dsRNA), cycloheximide and actinomycin D in FS11 cells. Arachidonic acid overcame the inhibitory effect of hydrocortisone on PGE production, but failed to restore IFN production in the presence of the steroid. Moreover, the prostaglandin synthetase inhibitors, indomethacin, aspirin and flufenamic acid, did not change IFN production by dsRNA in primed FSll cells, although prostaglandin synthesis was abolished. Although the induction of IFN and PGE by poly(rI).poly(rC) might be consequences of the same initial event in the cell, the accumulation of PGE does not seem to have a regulatory effect on the synthesis of IFN in this system.

Activities of the interferon system in patients with HBsAg‐positive chronic hepatitis B during short‐term steroid withdrawal therapy

“…A similar process may be involved regarding the HBV infected hepatocytes of the patients receiving PSL in the present study. On the other hand, a direct suppressive effect of hydrocortisone against in vitro IFN production has also been reported (21). Based on the present study, this inactivation of the IFN .system, which is one of the most important regulatory systems of viral replication in vivo (22)(23)(24)(25), also appears to contribute to the enhancement in HBV replication, as previously suggested (26).…”

The AU-rich sequences in the 3' untranslated region mediate the increased turnover of interferon mRNA induced by glucocorticoids.

“…Treatment with glucocorticoids inhibits production of IFN and increases the lethality of Coxsackie virus in infected mice (13)(14) . DEX decreases IFN production (15) and increases the turnover of IFN-O mRNA in human fibroblasts induced with double-stranded RNA and in murine C127 cells carrying an episomal vector for the constitutive expression of human IFN-O mRNA under the control of the herpes simplex virus thymidine kinase (tk) promotor (16). This mRNA does not contain the IFN-(3 5' untranslated region (UTR) (17), suggesting that the effect ofDEX is presumably mediated by coding or 3' UTR sequences .…”