Serum protein masking of the thermal sensitivity of the antiviral activity of purified human beta interferon: implications for clinical studies.
Human beta-interferon (HuIFN-beta) exhibits antiproliferative and antiviral properties. Successful clinical application of this drug depends on knowledge of the thermal stability of these activities under physiological conditions. In the present study, both the antiproliferative and antiviral activities were stabilized by the addition of very small quantities of serum proteins. This supplement was sufficient to mask the slightly higher thermosensitivity of the antiviral activity. In the absence of serum proteins, the values of both the half-life and the energy of activation were higher for the antiproliferative activity than for the antiviral function. Each had a half-life of at least 24 h and identical values for the energy of activation in the presence of proteins furnished by 1% fetal bovine serum. This study provides additional evidence to support a thesis recently advanced by Carter et al. that the antiproliferative domain of glycosylated beta interferon may be separable from the antiviral domain. It is concluded that the efficacy of HuIFN-beta, under clinical conditions, will not be seriously impaired by thermal inactivation. Antiviral assays of serum may be freely substituted for antiproliferative assays during pharmacological studies.
D001798:Blood Proteins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006131:Growth Inhibitors; D006358:Hot Temperature; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D009447:Neuroblastoma / Q000473:pathology; D013696:Temperature; D013816:Thermodynamics; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development; D014762:Viral Interference
D001798:Blood Proteins; D006131:Growth Inhibitors; D007370:Interferon Type I