Systemic and local interferon γ gene delivery to the lungs for treatment of allergen-induced airway hyperresponsiveness in mice

被引:72
作者
Dow, SW
Schwarze, J
Heath, TD
Potter, TA
Gelfand, EW
机构
[1] Univ Colorado, Hlth Sci Ctr, Dept Dermatol, Denver, CO 80262 USA
[2] Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA
[4] Univ Colorado, Hlth Sci Ctr, Ctr Canc, Denver, CO 80262 USA
[5] Natl Jewish Med & Res Ctr, Div Immunol, Dept Med, Denver, CO 80206 USA
[6] Natl Jewish Med & Res Ctr, Dept Pediat, Div Basic Sci, Denver, CO 80206 USA
关键词
D O I
10.1089/10430349950017266
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Allergen-induced airway hyperresponsiveness, an animal model of asthma in humans, may respond to immunotherapy with Th1 cytokines, For example, local administration of recombinant IL-12 or IFN-gamma, or intratracheal delivery of the genes for these cytokines, has been shown to reduce the severity of allergen-induced airway hyperresponsiveness (AHR) in rodent models, We reasoned that systemic cytokine gene delivery to the lungs by intravenous injection of lipid-DNA complexes might also be an effective approach to treatment of allergen-induced AHR. Therefore, the effects of either systemic or local pulmonary IFN-gamma gene delivery were evaluated in mice with allergen-induced AHR, The effects of treatment on AHR, airway eosinophilia and cytokine production, and serum IgE concentrations were evaluated in mice that were first sensitized to ovalbumin and then subjected to aerosol ovalbumin challenge. Intravenous IFN-gamma gene delivery significantly inhibited development of AHR and airway eosinophilia and decreased serum IgE levels, compared with control mice or mice treated with noncoding DNA, Intratracheal IFN-gamma gene delivery also significantly inhibited AHR and airway eosinophilia, but did not affect serum IgE levels. Treatment with recombinant IFN-gamma was much less effective than IFN-gamma gene delivery by either route. We conclude that either systemic or local pulmonary delivery of a Th1 cytokine gene such as IFN-gamma may be an effective approach for treatment of allergen-induced asthma.
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收藏
页码:1905 / 1914
页数:10
相关论文
共 31 条
[21]  
*NAT ASTHM ED PREV, 1997, NIH PUBL
[22]   Passive transfer of immediate hypersensitivity and airway hyperresponsiveness by allergen-specific immunoglobulin (Ig) E and IgG1 in mice [J].
Oshiba, A ;
Hamelmann, E ;
Takeda, K ;
Bradley, KL ;
Loader, JE ;
Larsen, GL ;
Gelfand, EW .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (06) :1398-1408
[23]   PREDOMINANT TH2-LIKE BRONCHOALVEOLAR LYMPHOCYTE-T POPULATION IN ATOPIC ASTHMA [J].
ROBINSON, DS ;
HAMID, Q ;
YING, S ;
TSICOPOULOS, A ;
BARKANS, J ;
BENTLEY, AM ;
CORRIGAN, C ;
DURHAM, SR ;
KAY, AB .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (05) :298-304
[24]  
SCHLEIMER RP, 1993, EUR J CLIN PHARM S1, V45, P3
[25]  
SCHUMACHER JH, 1988, J IMMUNOL, V141, P1576
[26]   Local treatment with IL-12 is an effective inhibitor of airway hyperresponsiveness and lung eosinophilia after airway challenge in sensitized mice [J].
Schwarze, J ;
Hamelmann, E ;
Cieslewicz, G ;
Tomkinson, A ;
Joetham, A ;
Bradley, K ;
Gelfand, EW .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1998, 102 (01) :86-93
[27]   A NOVEL SERIES OF AMPHIPHILIC IMIDAZOLINIUM COMPOUNDS FOR IN-VITRO AND IN-VIVO GENE DELIVERY [J].
SOLODIN, I ;
BROWN, CS ;
BRUNO, MS ;
CHOW, CY ;
JANG, EH ;
DEBS, RJ ;
HEATH, TD .
BIOCHEMISTRY, 1995, 34 (41) :13537-13544
[28]   Characterization of cationic liposome-mediated gene transfer in vivo by intravenous administration [J].
Song, YK ;
Liu, F ;
Chu, SY ;
Liu, DX .
HUMAN GENE THERAPY, 1997, 8 (13) :1585-1594
[29]   Improved DNA: Liposome complexes for increased systemic delivery and gene expression [J].
Templeton, NS ;
Lasic, DD ;
Frederik, PM ;
Strey, HH ;
Roberts, DD ;
Pavlakis, GN .
NATURE BIOTECHNOLOGY, 1997, 15 (07) :647-652
[30]   ALLERGIC AND NONALLERGIC ASTHMATICS HAVE DISTINCT PATTERNS OF T-CELL ACTIVATION AND CYTOKINE PRODUCTION IN PERIPHERAL-BLOOD AND BRONCHOALVEOLAR LAVAGE [J].
WALKER, C ;
BODE, E ;
BOER, L ;
HANSEL, TT ;
BLASER, K ;
VIRCHOW, JC .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1992, 146 (01) :109-115