Effect of murine recombinant IL-2 on the course of lupus-like disease in (NZB x NZW) F1 female mice

被引:3
作者
Ravel, G [1 ]
Christ, M
Ruat, C
Burnett, R
Descotes, J
机构
[1] MDS Pharma Serv, F-69210 St Germain sur lArbresle, France
[2] Hop Edouard Herriot, Poison Ctr, F-69437 Lyon 03, France
[3] Hop Edouard Herriot, INSERM U503, F-69437 Lyon 03, France
关键词
D O I
10.1081/IPH-120014726
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The exacerbation of pre-existing autoimmune diseases is a potential toxic effect of immunoactive drugs. An increase in the incidence of autoimmune thyroiditis has been noted in patients treated with human recombinant interleukin-2 (rIL-2). In contrast, human rIL-2 tends to protect mice from autoimmunity. As the effects of murine rIL-2 on autoimmunity have not been reported in mice, lupus-prone female (NZB x NZW) F1 mice were treated with 20,000 IU murine rIL-2 intraperitoneally, twice weekly for 13 weeks, beginning at 15 weeks of age. No evidence of an exacerbating effect of murine IL-2 on the lupus disease of (NZB x NZW) F, mice was observed as no change in the following parameters were seen, namely mean survival time, mean body weight, anti-DNA and antinuclear antibody production. These results show that: 1) like human rIL-2, murine rIL-2 does not exacerbate autoimmunity in mice; 2) the biological effects of human as well as murine rIL-2 in mice differ from those seen with human rIL-2 in man. These latter findings suggest that the selection of the relevant animal species for immunotoxicity studies with recombinant cytokines and derivatives may be less straightforward than previously thought.
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页码:409 / 421
页数:13
相关论文
共 31 条
[1]   INTERLEUKIN-2 ABROGATES THE NONRESPONSIVE STATE OF T-CELLS EXPRESSING A FORBIDDEN T-CELL RECEPTOR REPERTOIRE AND INDUCES AUTOIMMUNE-DISEASE IN NEONATALLY THYMECTOMIZED MICE [J].
ANDREUSANCHEZ, JL ;
DEALBORAN, IM ;
MARCOS, MAR ;
SANCHEZMOVILLA, A ;
MARTINEZ, C ;
KROEMER, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (06) :1323-1329
[2]  
BANERJEE S, 1988, J IMMUNOL, V141, P1150
[3]   The pathogenesis of autoimmunity in New Zealand mice [J].
Borchers, A ;
Ansari, AA ;
Hsu, T ;
Kono, DH ;
Gershwin, ME .
SEMINARS IN ARTHRITIS AND RHEUMATISM, 2000, 29 (06) :385-399
[4]   Autoimmunity induced by interferon-α therapy for chronic viral hepatitis [J].
Dumoulin, FL ;
Leifeld, L ;
Sauerbruch, T ;
Spengler, U .
BIOMEDICINE & PHARMACOTHERAPY, 1999, 53 (5-6) :242-254
[5]   INVIVO ADMINISTRATION OF INTERLEUKIN-2 TURNS ON ANERGIC SELF-REACTIVE T-CELLS AND LEADS TO AUTOIMMUNE-DISEASE [J].
GUTIERREZRAMOS, JC ;
DEALBORAN, IM ;
MARTINEZ, C .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (11) :2867-2872
[6]   RENAL DISEASE ASSOCIATED WITH POSITIVE LUPUS ERYTHEMATOSUS TESTS IN A CROSS-BRED STRAIN OF MICE [J].
HELYER, BJ ;
HOWIE, JB .
NATURE, 1963, 197 (486) :197-&
[7]  
Howie J B, 1968, Adv Immunol, V9, P215, DOI 10.1016/S0065-2776(08)60444-7
[8]   RESTORATION OF AN EARLY, PROGRESSIVE DEFECT IN RESPONSIVENESS TO T-CELL ACTIVATION IN LUPUS MICE BY EXOGENOUS IL-2 [J].
HUANG, FP ;
STOTT, DI .
AUTOIMMUNITY, 1993, 15 (01) :19-29
[9]   Modulation of autoimmune disease in the MRL-lpr/lpr mouse by IL-2 and TGF-β1 gene therapy using attenuated Salmonella typhimurium as gene carrier [J].
Huggins, ML ;
Huang, FP ;
Xu, D ;
Lindop, G ;
Stott, DI .
LUPUS, 1999, 8 (01) :29-38
[10]   UNIQUE STRUCTURE OF MURINE INTERLEUKIN-2 AS DEDUCED FROM CLONED CDNAS [J].
KASHIMA, N ;
NISHITAKAOKA, C ;
FUJITA, T ;
TAKI, S ;
YAMADA, G ;
HAMURO, J ;
TANIGUCHI, T .
NATURE, 1985, 313 (6001) :402-404