Abstract
1 Levels of IL-13, IL-1β and TNF-α are increased in bronchial lavage fluid of asthmatics and induce certain significant features of bronchial asthma including airway hyper-responsiveness (AHR). In this study, we have investigated the effect of these cytokines in naïve mice and those sensitized to ovalbumin (OVA) on bronchoconstrictions to methacholine (MCh) and the functional antagonism induced by β 2-adrenoceptor agonism. 2 Naïve or OVA-sensitized mice were treated for 3days with IL-1β (250U), TNF-α (150ng), IL-13 (5μg) or combinations of IL-1β with TNF-α or IL-1β with IL-13. MCh-induced bronchoconstriction and its sensitivity to albuterol, a β 2-adrenoceptor agonist, was assessed 24h after the last cytokine administration. 3 In naïve mice, responsiveness to MCh was significantly increased by the combination of IL-1β and TNF-α, IL-13 alone or in combination with IL-1β, but not by treatment with IL-1β or TNF-α alone. Similar results were obtained in OVA-sensitized mice except that treatment with IL-13 alone did not increase sensitivity to MCh. 4 In naïve mice, albuterol sensitivity was only significantly attenuated by treatment with IL-1β and TNF-α in combination. In mice sensitized to OVA, albuterol sensitivity was significantly attenuated by treatment with TNF-α, IL-13 or IL-13 in combination with IL-1β. 5 Inflammatory cell influx was increased by all cytokines and combinations except IL-13 in OVA-sensitized mice. 6 Our data do not support a link between inflammatory cell influx and AHR. In addition, the mechanism of IL-13-induced AHR might involve decreased β 2-adrenoceptor responsiveness.
| Original language | English |
|---|---|
| Pages (from-to) | 37-49 |
| Number of pages | 13 |
| Journal | Autonomic and Autacoid Pharmacology |
| Volume | 31 |
| Issue number | 3-4 |
| DOIs | |
| State | Published - Jul 2011 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
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Effect of IL-1β and TNF-αvs IL-13 on bronchial hyperresponsiveness, β 2-adrenergic responses and cellularity of bronchial alveolar lavage fluid. / Horiba, M.; Qutna, N.; Gendapodi, P.; Agrawal, S.; Sapkota, K.; Abel, Peter W.; Townley, R. G.
In: Autonomic and Autacoid Pharmacology, Vol. 31, No. 3-4, 07.2011, p. 37-49.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of IL-1β and TNF-αvs IL-13 on bronchial hyperresponsiveness, β 2-adrenergic responses and cellularity of bronchial alveolar lavage fluid
AU - Horiba, M.
AU - Qutna, N.
AU - Gendapodi, P.
AU - Agrawal, S.
AU - Sapkota, K.
AU - Abel, Peter W.
AU - Townley, R. G.
PY - 2011/7
Y1 - 2011/7
N2 - 1 Levels of IL-13, IL-1β and TNF-α are increased in bronchial lavage fluid of asthmatics and induce certain significant features of bronchial asthma including airway hyper-responsiveness (AHR). In this study, we have investigated the effect of these cytokines in naïve mice and those sensitized to ovalbumin (OVA) on bronchoconstrictions to methacholine (MCh) and the functional antagonism induced by β 2-adrenoceptor agonism. 2 Naïve or OVA-sensitized mice were treated for 3days with IL-1β (250U), TNF-α (150ng), IL-13 (5μg) or combinations of IL-1β with TNF-α or IL-1β with IL-13. MCh-induced bronchoconstriction and its sensitivity to albuterol, a β 2-adrenoceptor agonist, was assessed 24h after the last cytokine administration. 3 In naïve mice, responsiveness to MCh was significantly increased by the combination of IL-1β and TNF-α, IL-13 alone or in combination with IL-1β, but not by treatment with IL-1β or TNF-α alone. Similar results were obtained in OVA-sensitized mice except that treatment with IL-13 alone did not increase sensitivity to MCh. 4 In naïve mice, albuterol sensitivity was only significantly attenuated by treatment with IL-1β and TNF-α in combination. In mice sensitized to OVA, albuterol sensitivity was significantly attenuated by treatment with TNF-α, IL-13 or IL-13 in combination with IL-1β. 5 Inflammatory cell influx was increased by all cytokines and combinations except IL-13 in OVA-sensitized mice. 6 Our data do not support a link between inflammatory cell influx and AHR. In addition, the mechanism of IL-13-induced AHR might involve decreased β 2-adrenoceptor responsiveness.
AB - 1 Levels of IL-13, IL-1β and TNF-α are increased in bronchial lavage fluid of asthmatics and induce certain significant features of bronchial asthma including airway hyper-responsiveness (AHR). In this study, we have investigated the effect of these cytokines in naïve mice and those sensitized to ovalbumin (OVA) on bronchoconstrictions to methacholine (MCh) and the functional antagonism induced by β 2-adrenoceptor agonism. 2 Naïve or OVA-sensitized mice were treated for 3days with IL-1β (250U), TNF-α (150ng), IL-13 (5μg) or combinations of IL-1β with TNF-α or IL-1β with IL-13. MCh-induced bronchoconstriction and its sensitivity to albuterol, a β 2-adrenoceptor agonist, was assessed 24h after the last cytokine administration. 3 In naïve mice, responsiveness to MCh was significantly increased by the combination of IL-1β and TNF-α, IL-13 alone or in combination with IL-1β, but not by treatment with IL-1β or TNF-α alone. Similar results were obtained in OVA-sensitized mice except that treatment with IL-13 alone did not increase sensitivity to MCh. 4 In naïve mice, albuterol sensitivity was only significantly attenuated by treatment with IL-1β and TNF-α in combination. In mice sensitized to OVA, albuterol sensitivity was significantly attenuated by treatment with TNF-α, IL-13 or IL-13 in combination with IL-1β. 5 Inflammatory cell influx was increased by all cytokines and combinations except IL-13 in OVA-sensitized mice. 6 Our data do not support a link between inflammatory cell influx and AHR. In addition, the mechanism of IL-13-induced AHR might involve decreased β 2-adrenoceptor responsiveness.
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U2 - 10.1111/j.1474-8673.2011.00465.x
DO - 10.1111/j.1474-8673.2011.00465.x
M3 - Article
VL - 31
SP - 37
EP - 49
JO - Autonomic and Autacoid Pharmacology
JF - Autonomic and Autacoid Pharmacology
SN - 1474-8665
IS - 3-4
ER -