Double-Blind Randomized Phase I Study on the Clinical Tolerance and Biological Effects of Natural and Recombinant Interferon-β

Abstract

The clinical tolerance of and the effects recombinant human interferon-beta (rHuIFN-beta) obtained from mammalian cells (Chinese hamster ovary cells) exerts on 2',5'-oligoadenyl (2-5A) synthetase activity, human-Mx protein, neopterin, beta 2-microglobulin, interleukin-1 (IL-1) alpha and beta synthesis were compared to those of natural IFN-beta in 12 healthy volunteers. Each subject received a single i.m. injection of 6 x 10(6) IU rHuIFN-beta and natural IFN-beta according to a randomized double-blind cross-over study design. Both were well tolerated and provoked similar changes in clinical indices. Moreover, rHuIFN-beta and natural IFN-beta induced significant and similar increases in 2'-5' adenylates, human Mx protein, and neopterin levels, but neither modulated beta 2-microglobulin, IL-1 alpha or beta synthesis. The sum of these findings indicates that rHuIFN-beta and natural IFN-beta are biologically equivalent. In view of these results, we are of the opinion that these two types of IFN are probably also therapeutically equivalent and, in consequence, that trials to evaluate the response of viral and neoplastic disease patients to rHuIFN-beta are fully justified.

Radiosensitizing effect of natural and recombinant β-interferons in a human lung carcinoma in vitro

“…However, higher concentrations of r-IFN-b-1b are needed in vitro as compared to n-IFN or r-IFN-b-1a to obtain an isoeective cytotoxic or radiosensitizing eect. Interestingly, n-IFN and r-IFN-b1a have displayed similar pharmacokinetic properties in clinical studies (Liberati et al 1992;Salmon et al 1996). A comparative study on the pharmacokinetics of r-IFNb-1a and r-IFN-b-1b has not been reported.…”

“…In a clinical study on healthy volunteers, recombinant IFN-b1b as compared to n-IFN-b induced similar changes in 2¢-5¢-adenylates, human Mx protein, and neopterin levels (Liberati et al 1992), which are considered to be the biochemical equivalent of the IFNaction. However, at present it is not clear whether the modulating action of IFNs on the radiation response is similar for natural as compared to recombinant IFNs.…”

Studies on the biological effects of ozone: 5. Evaluation of immunological parameters and tolerability in normal volunteers receiving ambulatory autohaemotherapy

“…That is the reason why we have explored possible changes in immunological parameters that may be more sensitive markers of cell activation. Indeed the expression of Mx protein in PBMC induced by IFNcx is a fairly long-lasting process [25,26] in comparison to cytokine's turnover. To our knowledge this is the first report showing that autohaemotherapy carried out with our procedure [21], i.e., …”

“…Most of the peaks occur earlier, i.e., at 48 hours, although the 5th peak is delayed by 72 hours. After a parenteral injection of either a or/3IFNs the Mx proteins peak occurs usually after 24 hours [25,26] but, after autohaemotherapy, PBMC, after homing in various organs, are likely to release IFN for 1-2 days therefore delaying the maximal expression of Mx proteins in circulating PBMC.…”