Recombinant interferons beta and gamma have a higher antiviral activity than interferon-alpha in coxsackievirus B3-infected carrier state cultures of human myocardial fibroblasts

被引:27
作者
Heim, A [1 ]
StilleSiegener, M [1 ]
PringAkerblom, P [1 ]
Grumbach, I [1 ]
Brehm, C [1 ]
Kreuzer, H [1 ]
Figulla, HR [1 ]
机构
[1] UNIV GOTTINGEN,ABT KARDIOL,D-37075 GOTTINGEN,GERMANY
关键词
D O I
10.1089/jir.1996.16.283
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We compared the antiviral activities of three recombinant human interferons (IFN-alpha 2a, IFN-beta, and IFN-gamma) in cultured human myocardial fibroblasts to select a candidate for trial in heart disease induced by cardiotropic enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and after 7 days, when a persistent infection had developed, IFN was added. Virus yields were measured on alternate days for the next 7 or 16 days, and IFN activity was assessed as the percentage reduction in yield. IFN-gamma and IFN-beta were both highly active and reduced virus yields by 2 log (EC(99)) at concentrations of 23.4 IU/ml (SD = 8.6) and 10.1 IU/ml (SD = 3.2), respectively; with 250 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, IFN-alpha 2a (EC(99) > 1250 IU/ml) was at least 120 times less active than IFN-beta; after use for 8 days or more, the minor effects it produced were no longer related to the concentration applied. Despite the pharmacokinetic advantages of IFN-alpha 2a, our data suggest that IFN-beta should in preference be evaluated in the clinic.
引用
收藏
页码:283 / 287
页数:5
相关论文
共 41 条
[1]   DIFFERENTIAL TYROSINE PHOSPHORYLATION OF THE IFNAR CHAIN OF THE TYPE-I INTERFERON RECEPTOR AND OF AN ASSOCIATED SURFACE PROTEIN IN RESPONSE TO IFN-ALPHA AND IFN-BETA [J].
ABRAMOVICH, C ;
SHULMAN, LM ;
RATOVITSKI, E ;
HARROCH, S ;
TOVEY, M ;
EID, P ;
REVEL, M .
EMBO JOURNAL, 1994, 13 (24) :5871-5877
[2]   MULTIPLE-DRUG EFFECT ANALYSIS WITH CONFIDENCE-INTERVAL [J].
BELENKII, MS ;
SCHINAZI, RF .
ANTIVIRAL RESEARCH, 1994, 25 (01) :1-11
[3]  
BENOIT P, 1993, J IMMUNOL, V150, P707
[4]   GAMMA-INTERFERON - THE MATCH THAT LIGHTS THE FIRE [J].
BILLIAU, A .
IMMUNOLOGY TODAY, 1988, 9 (02) :37-40
[5]   PHARMACOLOGY AND SIDE-EFFECTS OF INTERFERONS [J].
BOCCI, V .
ANTIVIRAL RESEARCH, 1994, 24 (2-3) :111-119
[6]  
CAPOBIANCHI M R, 1991, Viral Immunology, V4, P103, DOI 10.1089/vim.1991.4.103
[7]   QUANTITATIVE-ANALYSIS OF DOSE-EFFECT RELATIONSHIPS - THE COMBINED EFFECTS OF MULTIPLE-DRUGS OR ENZYME-INHIBITORS [J].
CHOU, TC ;
TALALAY, P .
ADVANCES IN ENZYME REGULATION, 1984, 22 :27-55
[8]  
COLAMONICI OR, 1994, J BIOL CHEM, V269, P3518
[9]   JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS [J].
DARNELL, JE ;
KERR, IM ;
STARK, GR .
SCIENCE, 1994, 264 (5164) :1415-1421
[10]   RAPID COLORIMETRIC ASSAY FOR CELL-GROWTH AND SURVIVAL - MODIFICATIONS TO THE TETRAZOLIUM DYE PROCEDURE GIVING IMPROVED SENSITIVITY AND RELIABILITY [J].
DENIZOT, F ;
LANG, R .
JOURNAL OF IMMUNOLOGICAL METHODS, 1986, 89 (02) :271-277