(2′-5′)O1igo(A) Synthetase as a Monitor of Interferon Action in Juvenile Laryngeal Papillomatosis

Abstract

Four children with juvenile laryngeal papillomatosis were treated with human leukocyte interferon (IFN-alpha) by intravenous infusions. In three cases the clinical course of the disease was effected favorably. Serum IFN titers and (2'-5')oligo(A) synthetase (OAS) levels in lymphocytes of the patients were measured once a week during therapy. Levels of serum IFN determined 15 min after the end of 1 h infusions corresponded to only 15%-40% of the amount infused. Comparable OAS activities in the four children were measured before infusion, i.e., one, two, or three days, respectively, after the preceding infusion, though mean IFN titers of the patients differed from each other (200-400 and 400-600 u/ml). This suggests a saturation of the lymphocytes' antiviral system by these IFN levels. A discontinuation for two weeks in the early phase of IFN treatment, accompanied by a decrease of the OAS activity in the lymphocytes to the basal level, resulted in a deterioration of the patient's condition. A change in treatment schedule causing a decrease of OAS activity to a lower, though still elevated level, for six weeks until the present did not influence the course of therapy. Therefore, we suppose that the maintenance of elevated levels of OAS activity in lymphocytes for some months may be a necessary, even though not always a sufficient, criterion for a successful therapy schedule in IFN treatment of juvenile laryngeal papillomatosis. In addition, our results suggest OAS activity to be suitable in monitoring effects of an IFN therapy.

MxA Gene Expression after Live Virus Vaccination: A Sensitive Marker for Endogenous Type I Interferon

“…Several IFN-inducible genes are activated by type I and type II IFNs. Their products have previously been used as markers for IFN [6,8,12,22,23]. We therefore determined in parallel the kinetics of the three most widely used IFN markers.…”

“…Increased levels of an IFN-induced gene product indicate that the cells have been exposed to IFN in vivo and are respond-ing to it. One of the most widely used assays measures the induction ofan intracellular enzyme, 2',5'-oligoadenylate (2-SA) synthetase [6][7][8]. This enzyme assay is considered to be more sensitive than IFN measurements in serum [6] and has the additional advantage that elevated enzyme activities remain detectable long after IFN has disappeared from the blood [9].…”

Methods for the Determination of the Interferon-Induced Enzyme 2'-5' Oligoadenylate Synthetase in Mononuclear Blood Cells

“…Comparison between the Schattner assay (16) and the assays of Lodemann (14) and Ball (17) The common feature of these three assays is that 2'-5'-oligoadenylates formed during the 2'-5'-oligoadenylate synthetase reaction are converted into the corresponding 2 / -5 / -oligoadenylate cores by treatment with bacterial alkaline phosphatase (fig. 2); this allows an easier Separation of the reaction products.…”

“…1) biological assays (RNA-cleavage assay (21-23), protein synthesis Inhibition assay (24)) 2) binding assays (radiobinding assay (l 5), radioimmunoassay (25), enzymeimmunoassay (26,27)) and 3) assays that determine 2 / -5'-oligoadenylates formed during the 2 / -5'-oligoadenylate synthetase reaction (14,16,17,28,29).…”

“…It shows an especially marked elevation after interferon treatment. Therefore, the determination of 2'-5'-oligoadenylate synthetase has been widely used in the diagnosis of different diseases connected with the interferon System (5 -12) and äs a response parameter during interferon therapy (13,14). Several methods for the determination of 2'-5'-oligpadenylate synthetase in different cell types have been described (for review see 1. c. (1)).…”