Recombinant Murine Interferon-beta Research Articles

Inhibition of lung colonization of mouse colon 26 adenocarcinoma by recombinant mouse interferon ? through a modification of platelet function

Recombinant murine interferon beta (MuIFN-beta) given i.v. efficiently inhibited both pulmonary arrest and formation of lung colonies of NL-17, a highly metastatic variant of mouse colon adenocarcinoma 26. NL-17 was rather resistant to MuIFN-beta in vitro and was highly resistant to natural killer cells of mice even though they were treated in vivo with MuIFN-beta. Platelets isolated from MuIFN-beta-treated mice showed reduced aggregating activity induced by NL-17. Since lung colonization by NL-17 is influenced by platelet aggregation, the inhibition of colonization by MuIFN-beta could be partly mediated through modification of platelet function in vivo. The effect of MuIFN-beta on platelet function and its subsequent inhibition of lung colony formation give new insights into the action of recombinant MuIFN-beta.

Protective effect of recombinant murine interferon beta against mouse hepatitis virus infection

Recombinant murine interferon beta (rMuIFN-β) protected susceptible C57BL/6 mice against lethal mouse hepatitis virus (MHV) infection. rMuIFN-β was life saving if it was given intraperitoneally beginning 21 h before infection and daily thereafter for 9 days, and lengthened the survival time if given from 3 h after infection. rMuIFN-β treatment beginning 24 h after infection was ineffective. The survival rate was dose-dependent, and the 50% effective dose of rMuIFN-β for survival was 1780 IU per day. rMuIFN-β pretreatment inhibited virus growth completely in the brain and moderately in the liver and spleen and prevented severe hepatic lesions. rMuIFN-β also protected beige mice and cyclophosphamide-treated mice against MHV infection, suggesting that activation of natural killer cells or T-cells by rMuIFN-β is not critical for protection.

Antitumor effect of recombinant murine interferon-beta against mouse malignant glioma.

A study was made on the antitumor effect of recombinant murine interferon-beta (rMuIFN-beta) against virus-induced mouse malignant glioma. In in vitro experiments, a dose-dependent and a time-dependent manner were observed for 24 h in the antiproliferative activity of rMuIFN-beta. In in vitro experiments, the growth of subcutaneously transplanted gliomas in mice treated with intraperitoneal administration of rMuIFN-beta was inhibited slightly, whereas, with intratumoral administration, it was inhibited more effectively. In immunological studies, natural killer (NK) cell and cytotoxic T-lymphocyte activities of spleen cells were enhanced with intraperitoneal administration of rMuIFN-beta. The analysis of IFN-induced change in a subpopulation of peripheral blood lymphocytes revealed a decrease of Thy.1,2-positive cells and an increase in the ratio of Lyt.1/Lyt.2-positive cells. But these immunological effects of rMuIFN-beta declined on the 7th day with daily administration. Such hyporeactivity may be noteworthy for the clinical application of IFN.

Antitumour effect of interferon combined with hyperthermia against experimental brain tumour.

Antiproliferative activity of recombinant murine interferon-beta (Rec-MuIFN-beta) combined with hyperthermia against Rous sarcoma virus-induced mouse malignant glioma (RSV glioma) was investigated both in vitro and in vivo. In vitro, the antiproliferative activity of Rec-MuIFN-beta was enhanced by incubation at elevated temperatures (40 degrees and 43 degrees C). In vivo, combined therapy of Rec-MuIFN-beta treatment and local tumour hyperthermia (43 degrees C) exerted a greater antitumour effect against transplanted RSV glioma in C3H/He mice than either treatment alone, especially when Rec-MuIFN-beta was administered intratumourally. Subsequently, in order to probe the mechanism of enhanced antiproliferative activity, the production of prostaglandin E2 (PGE2) and 2', 5'-oligoadenylate synthetase (2-5A synthetase) in the culture medium of RSV glioma cells was measured. Rec-MuIFN-beta treatment resulted in a significantly greater PGE2 and 2-5A synthetase production at 43 degrees C than at 37 degrees C.

Crystallization and preliminary X-ray studies of recombinant murine interferon-beta.

Recombinant murine interferon-beta produced in Escherichia coli was purified and crystallized in an orthorhombic space group C222(1) with a = 61.67 A, b = 55.62 A, and c = 92.16 A. The crystals with a slight tendency for orientational disorder around the c axis diffract at least up to 3.3-A resolution. The crystallizability and the fact that the crystallographic asymmetric unit contains only one molecule of murine interferon-beta strongly indicate that the present preparation (Matsuda, S., Utsumi, J., and Kawano, G. (1986) J. Interferon Res., in press) of recombinant murine interferon-beta is predominantly homogeneous with respect to chemical, tertiary, and quaternary structures.