Respiratory syncytial virus infection does not increase allergen-induced type 2 cytokine production, yet increases airway hyperresponsiveness in mice

被引:16
作者
Peebles, RS
Sheller, JR
Collins, RD
Jarzecka, AK
Mitchell, DB
Parker, RA
Graham, BS
机构
[1] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA
[4] Harvard Univ, Sch Med, Dept Med Biostat, Boston, MA USA
关键词
airway hyperresponsiveness; immunoglobulin E; respiratory syncytial virus; bronchoalveolar lavage; periodic acid-Schiff; interleukin; interferon;
D O I
10.1002/1096-9071(20000201)63:2<178::AID-JMV1013>3.3.CO;2-F
中图分类号
Q93 [微生物学];
学科分类号
071005 [微生物学]; 100705 [微生物与生化药学];
摘要
Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined murine models of allergen sensitization and RSV infection to explore the interaction of allergic and virus-induced airway inflammation and its impact on airway hyperresponsiveness (AHR). We found that RSV infection during ova-sensitization (OVA/RSV) increased and prolonged AHR compared to mice only RSV-infected (RSV) or ova-sensitized (OVA). AHR is known to be associated with an increase in Type 2 cytokines (IL-4, IL-5, and IL-13) in allergen-sensitized mice. Therefore, we hypothesized that RSV-induced enhancement of AHR was a result of potentiating the Type 2 cytokine profile promoted by ova-sensitization. Surprisingly, we found that Type 2 cytokines induced by ova-sensitization were not increased by RSV infection despite the increase in AHR, and in some cases were diminished. RNAse protection assay revealed no difference in IL-4 and IL-5 mRNA levels between the OVA and OVA/RSV groups, and IL-13 mRNA was significantly decreased in the OVA/RSV mice compared to the OVA group. Flow cytometric analysis of Type 2 cytokines demonstrated the same frequency of IL-4 and IL-5 production in lung-derived T lymphocytes from the OVA/RSV and OVA groups. Direct cytokine ELISA measurements of lung supernatant showed the level of IL-13 was significantly decreased in the OVA/RSV group compared to OVA mice, while there was no difference in either IL-4 or IL-5 between these two groups. These data indicate that the enhanced and prolonged AHR caused by the interaction of allergic airway inflammation and virus-induced immune responses is a complex process that can not be explained simply by augmented production of Type 2 cytokines. (C) 2001 Wiley-Liss, Inc.
引用
收藏
页码:178 / 188
页数:11
相关论文
共 42 条
[1]
MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA ACTIVATES BASOPHILS AND MAST-CELLS [J].
ALAM, R ;
FORSYTHE, PA ;
STAFFORD, S ;
LETTBROWN, MA ;
GRANT, JA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (03) :781-786
[2]
DISTINCT TYPES OF LUNG-DISEASE CAUSED BY FUNCTIONAL SUBSETS OF ANTIVIRAL T-CELLS [J].
ALWAN, WH ;
KOZLOWSKA, WJ ;
OPENSHAW, PJM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (01) :81-89
[3]
Respiratory tract viral infections in inner-city asthmatic adults [J].
Atmar, RL ;
Guy, E ;
Guntupalli, KK ;
Zimmerman, JL ;
Bandi, VD ;
Baxter, BD ;
Greenberg, SB .
ARCHIVES OF INTERNAL MEDICINE, 1998, 158 (22) :2453-2459
[4]
Bembridge GP, 1998, J IMMUNOL, V161, P2473
[5]
ATTENUATION OF ALLERGIC AIRWAY INFLAMMATION IN IL-4 DEFICIENT MICE [J].
BRUSSELLE, GG ;
KIPS, JC ;
TAVERNIER, JH ;
VANDERHEYDEN, JG ;
CUVELIER, CA ;
PAUWELS, RA ;
BLUETHMANN, H .
CLINICAL AND EXPERIMENTAL ALLERGY, 1994, 24 (01) :73-80
[6]
ROLE OF LEUKOTRIENES REVEALED BY TARGETED DISRUPTION OF THE 5-LIPOXYGENASE GENE [J].
CHEN, XS ;
SHELLER, JR ;
JOHNSON, EN ;
FUNK, CD .
NATURE, 1994, 372 (6502) :179-182
[7]
Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity [J].
Corry, DB ;
Folkesson, HG ;
Warnock, ML ;
Erle, DJ ;
Matthay, MA ;
WienerKronish, JP ;
Locksley, RM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (01) :109-117
[8]
INTERLEUKIN-4 IS REQUIRED FOR THE INDUCTION OF LUNG TH2 MUCOSAL IMMUNITY [J].
COYLE, AJ ;
LEGROS, G ;
BERTRAND, C ;
TSUYUKI, S ;
HEUSSER, CH ;
KOPF, M ;
ANDERSON, GP .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1995, 13 (01) :54-59
[9]
VIRUS-SPECIFIC CD8(+) CELLS CAN SWITCH TO INTERLEUKIN-5 PRODUCTION AND INDUCE AIRWAY EOSINOPHILIA [J].
COYLE, AJ ;
ERARD, F ;
BERTRAND, C ;
WALTI, S ;
PIRCHER, H ;
LEGROS, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (03) :1229-1233
[10]
Sorting out the cytokines of asthma [J].
Drazen, JM ;
Arm, JP ;
Austen, KF .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (01) :1-5