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Adoptively transferred late allergic airway responses are associated with Th2-type cytokines in the rat.

https://arctichealth.org/en/permalink/ahliterature57629
Source
Am J Respir Cell Mol Biol. 1997 Jan;16(1):69-74
Publication Type
Article
Date
Jan-1997
Author
A. Watanabe
H. Mishima
T C Kotsimbos
M. Hojo
P M Renzi
J G Martin
Q A Hamid
Author Affiliation
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Source
Am J Respir Cell Mol Biol. 1997 Jan;16(1):69-74
Date
Jan-1997
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Airway Resistance
Animals
Bronchoalveolar Lavage Fluid - cytology - immunology
CD4-Positive T-Lymphocytes - immunology - transplantation
CD8-Positive T-Lymphocytes - immunology - transplantation
Interferon Type II - biosynthesis
Interleukin-2 - biosynthesis
Interleukin-4 - biosynthesis
Interleukin-5 - biosynthesis
Interleukins - biosynthesis
Ovalbumin - immunology
Rats
Research Support, Non-U.S. Gov't
Respiratory Hypersensitivity - immunology
Th2 Cells - immunology
Abstract
Late allergic airway responses can be transferred by CD4+ T cells in the rat. To investigate the role of T-cell cytokines in these responses, we examined the expression of mRNA for Th2 (interleukin [IL]-4 and IL-5) and Th1 (IL-2 and interferon gamma [INF-gamma])-type cytokines in Brown Norway rats that were administered either antigen-primed W3/25(CD4)+ or OX8(CD8)+ T cells. Donors were actively sensitized by subcutaneous injection of ovalbumin (OVA) in the neck and T cells were obtained from the cervical lymph nodes by immunomagnetic cell sorting for administration to unsensitized rats. Control rats received bovine serum albumin (BSA)-primed CD4+ and CD8+ T cells. Two days later, recipient rats were challenged with aerosolized OVA, and bronchoalveolar lavage (BAL) was performed 8 h after challenge. BAL cells expressing mRNA for IL-2, IL-4, IL-5, and INF-gamma were analyzed using the technique of in situ hybridization. Recipients of OVA-primed CD4+ T cells had an increase in the fraction of BAL cells expressing mRNA for IL-4 and IL-5 compared with BSA-primed CD4+ or OVA-primed CD8+ cells (P
PubMed ID
8998081 View in PubMed
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Adoptively transferred late allergic response is inhibited by IL-4, but not IL-5, antisense oligonucleotide.

https://arctichealth.org/en/permalink/ahliterature15653
Source
J Allergy Clin Immunol. 1999 Jul;104(1):205-14
Publication Type
Article
Date
Jul-1999
Author
S. Molet
D. Ramos-Barbón
J G Martin
Q. Hamid
Author Affiliation
Meakins-Christie Laboratories, McGill University, Montréal, Quebec, Canada.
Source
J Allergy Clin Immunol. 1999 Jul;104(1):205-14
Date
Jul-1999
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Asthma - immunology - prevention & control
Bronchoalveolar Lavage Fluid - chemistry - cytology
CD4-Positive T-Lymphocytes - drug effects
Cell Survival
Cells, Cultured
Cytokines - immunology
Disease Models, Animal
Immunohistochemistry
Interleukin-4 - immunology - therapeutic use
Interleukin-5 - immunology - therapeutic use
Male
Oligonucleotides, Antisense - therapeutic use
Ovalbumin - pharmacology
Pulmonary Eosinophilia - metabolism
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Th2 Cells - immunology
Abstract
BACKGROUND: We have shown previously that the late airways response (LAR) can be transferred by ovalbumin-primed CD4(+) T lymphocytes in Brown Norway rats. This response is associated with an increase of eosinophils and high expression of TH2 cytokines (IL-4 and IL-5) in bronchoalveolar lavage (BAL) fluid. OBJECTIVE: In this study we hypothesized that the inhibition of IL-4 or IL-5 production in the CD4(+) cells transferred to a naive animal could decrease the LAR and prevent airway eosinophilia in response to antigen challenge. METHODS: CD4(+) cells, purified from the cervical lymph nodes of ovalbumin-sensitized rats, were maintained in culture for 6 hours with medium alone or with 10 microgram/mL IL-4 antisense (AS), IL-5 AS, or control AS oligodeoxynucleotide. Then the cells were administrated intraperitoneally to naive rats, which were challenged 2 days later by a 5% ovalbumin aerosol. The lung resistance was measured for 8 hours, and then BAL was performed. Cytospin preparations from BAL cells were assessed for the presence of eosinophils by immunocytochemistry for major basic protein and for IL-4, IL-5, and IFN-gamma expression. RESULTS: In rats injected with IL-4 AS-treated T cells, LAR, eosinophils, and IL-4 and IL-5 expression were significantly decreased compared with the other groups. Only IL-5 expression in BAL fluid was slightly decreased consequent to the transfer of IL-5 AS-treated T cells. CONCLUSION: This study demonstrates that, in the CD4(+) T cell-driven LAR, the early production of IL-4, but not IL-5, by the transferred CD4(+) cells is essential for the development of the LAR.
Notes
Erratum In: J Allergy Clin Immunol 1999 Dec;104(6):1188
PubMed ID
10400863 View in PubMed
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Adoptive transfer of allergic airway responses with sensitized lymphocytes in BN rats.

https://arctichealth.org/en/permalink/ahliterature57674
Source
Am J Respir Crit Care Med. 1995 Jul;152(1):64-70
Publication Type
Article
Date
Jul-1995
Author
A. Watanabe
P. Rossi
P M Renzi
L J Xu
R D Guttmann
J G Martin
Author Affiliation
Meakins-Christie Laboratories, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada.
Source
Am J Respir Crit Care Med. 1995 Jul;152(1):64-70
Date
Jul-1995
Language
English
Publication Type
Article
Keywords
Animals
Bronchial Hyperreactivity - immunology - physiopathology
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - cytology
Eosinophils - immunology
Immunoglobulin E - immunology
Immunotherapy, Adoptive
Male
Ovalbumin - immunology
Passive Cutaneous Anaphylaxis - immunology
Rats
Rats, Inbred BN
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
Respiratory Hypersensitivity - immunology - physiopathology
Serum Albumin, Bovine - immunology
T-Lymphocytes - immunology
Abstract
To evaluate the role of lymphocytes in the pathogenesis of allergic bronchoconstriction, we investigated whether allergic airway responses are adoptively transferred by antigen-primed lymphocytes in Brown Norway (BN) rats. Animals were actively sensitized to ovalbumin (OA) or sham sensitized, and 14 d later mononuclear cells (MNCs) were isolated from intrathoracic lymph nodes, passed through a nylon wool column, and transferred to naive syngeneic rats. Recipients were challenged with aerosolized OA or bovine serum albumin (BSA) (5% wt/vol) and analyzed for changes in lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), and bronchoalveolar lavage (BAL) cells. Recipients of MNCs from sensitized rats responded to OA inhalation and exhibited sustained increases in RL throughout the 8-h observation period, but without usual early airway responses. Recipients of sham-sensitized MNCs or BSA-challenged recipients failed to respond to antigen challenge. At 32 h after OA exposure, airway responsiveness to MCh was increased in four of seven rats that had received sensitized MNCs (p = 0.035). BAL eosinophils increased at 32 h in the recipients of both sensitized and sham-sensitized MNCs. However, eosinophil numbers in BAL were inversely correlated with airway responsiveness in the recipients of sensitized MNCs (r = -0.788, p = 0.036). OA-specific immunoglobulin E (IgE) was undetectable by enzyme-linked immunosorbent assay (ELISA) or passive cutaneous anaphylaxis (PCA) in recipient rats following adoptive transfer. In conclusion, allergic late airway responses (LAR) and cholinergic airway hyperresponsiveness, but not antigen-specific IgE and early responses, were adoptively transferred by antigen-primed lymphocytes in BN rats.(ABSTRACT TRUNCATED AT 250 WORDS)
PubMed ID
7599864 View in PubMed
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Antigen challenge of sensitized rats increases airway responsiveness to methacholine.

https://arctichealth.org/en/permalink/ahliterature16166
Source
J Appl Physiol. 1988 Oct;65(4):1642-6
Publication Type
Article
Date
Oct-1988
Author
S. Bellofiore
J G Martin
Author Affiliation
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Source
J Appl Physiol. 1988 Oct;65(4):1642-6
Date
Oct-1988
Language
English
Publication Type
Article
Keywords
Airway Resistance - drug effects
Animals
Antigens - immunology
Asthma - immunology - physiopathology
Immunization
Male
Methacholine Chloride
Methacholine Compounds - pharmacology
Ovalbumin - administration & dosage - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Abstract
We measured airway responsiveness to methacholine (MCh) of highly inbred rats before and after six inhalational challenges with antigen. Ten Brown-Norway rats (130-216 g) that were actively sensitized to ovalbumin (OA) received six challenges with OA at 5-day intervals beginning 19 days after sensitization. An aerosol of OA (5% wt/vol) was inhaled for 1, 2, 5, and 10 min or until pulmonary resistance (RL) increased by at least 50%. Challenges with aerosolized MCh were performed immediately before and 14 days after sensitization, 2 days after the 3rd OA exposure, and 2, 7, 12, and 17 days after the 6th OA challenge. Four unsensitized rats underwent inhalational challenges with MCh over an equivalent time period. Responsiveness to MCh was calculated as the concentration of MCh required to increase RL to 200% of the control value (EC200RL). Seven out of 10 rats in the experimental group reacted to the first OA challenge with an immediate increase in RL of greater than 50% of control (range 70-550%). Three animals were unreactive to OA. Base-line EC200RL for all rats undergoing sensitization was 2.13 mg/ml (geometric mean), and it did not change significantly after sensitization (2.05 mg/ml). However, EC200RL of the rats that reacted to OA (n = 7) decreased significantly after 3 (1.11 mg/ml; P less than 0.005) and 6 OA exposures (0.96 mg/ml; P less than 0.005). The increase in responsiveness to inhaled MCh was present 17 days after the last OA exposure (EC200RL = 1.40 mg/ml; P less than 0.05). EC200RL of neither the unreactive sensitized rats (n = 3) nor the control rats (n = 4) changed after OA challenges.(ABSTRACT TRUNCATED AT 250 WORDS)
PubMed ID
3053586 View in PubMed
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CD4+ T cells can induce airway hyperresponsiveness to allergen challenge in the brown norway rat.

https://arctichealth.org/en/permalink/ahliterature57554
Source
Am J Respir Crit Care Med. 1998 Dec;158(6):1863-70
Publication Type
Article
Date
Dec-1998
Author
H. Mishima
M. Hojo
A. Watanabe
Q A Hamid
J G Martin
Author Affiliation
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, and the Respiratory Health Network of Centres of Excellence, Montreal, Quebec, Canada.
Source
Am J Respir Crit Care Med. 1998 Dec;158(6):1863-70
Date
Dec-1998
Language
English
Publication Type
Article
Keywords
Aerosols
Allergens - immunology
Animals
Bronchial Hyperreactivity - immunology
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - chemistry - immunology
Bronchoconstrictor Agents - diagnostic use
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Cattle
Comparative Study
Eosinophilia - immunology
Gene Expression Regulation
Immunization
Immunoglobulin E - immunology
In Situ Hybridization
Interferon Type II - genetics - immunology
Interleukin-5 - genetics - immunology
Male
Methacholine Chloride - diagnostic use
Ovalbumin - immunology
Proteins - analysis
RNA, Messenger - genetics
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Serum Albumin, Bovine - immunology
Time Factors
Abstract
Airway hyperresponsiveness to inhalational challenge with methacholine (MCh) develops by 32 h after allergen challenge of actively sensitized BN rats. To test the hypothesis that CD4+ T cells mediate allergen-induced hyperresponsiveness independent of IgE-mediated mechanisms, we administered CD4+ T cells, CD8+ T cells, and a mixture of CD4+ and CD8+ T cells (total T cells) isolated from the cervical lymph nodes of rats sensitized with ovalbumin (OA) to naive BN rats that underwent aerosol challenge with either OA or bovine serum albumin (BSA) 2 d later. Responsiveness to MCh was measured 2 d before transfer of T cells and 32 h after challenge with OA or BSA. Airway responsiveness increased significantly in recipients of CD4+ T cells after OA challenge, but not in any other of the treatment groups. Analysis of bronchoalveolar lavage (BAL) cells for major basic protein expression by immunostaining showed eosinophilia in OA-challenged CD4+ and total T-cell recipients. Cells retrieved by bronchoalveolar lavage showed increased expression of IL-5 mRNA (in situ hybridization) in CD4+ T cell recipients after OA challenge compared with other groups. Interferon-gamma mRNA was expressed to the greatest extent in CD8+ recipients, but it was elevated in both OA- and BSA-challenged animals. We conclude that CD4+ T cells can induce airway hyperresponsiveness after inhalational challenge with allergen and this is associated with IL-5 production and eosinophilia. CD8+ T cells may have a negative regulatory effect on responsiveness, possibly mediated by interferon-gamma.
PubMed ID
9847279 View in PubMed
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CD8+ T cells modulate late allergic airway responses in Brown Norway rats.

https://arctichealth.org/en/permalink/ahliterature57532
Source
J Immunol. 1999 Nov 15;163(10):5574-81
Publication Type
Article
Date
Nov-15-1999
Author
M. Suzuki
R. Taha
D. Ihaku
Q. Hamid
J G Martin
Author Affiliation
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Source
J Immunol. 1999 Nov 15;163(10):5574-81
Date
Nov-15-1999
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - cytology - immunology
CD8-Positive T-Lymphocytes - immunology - metabolism - transplantation
Cytokines - biosynthesis
Flow Cytometry
Hypersensitivity, Delayed - immunology
Immunoglobulin E - blood
Leukocytes, Mononuclear - cytology - immunology
Lymph Nodes - cytology - immunology - metabolism
Lymphocyte Count
Lymphocyte Subsets - cytology - immunology
Male
Ovalbumin - blood - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Spleen - cytology - immunology - metabolism
Abstract
To test the hypothesis that CD8+ T cells may suppress the allergen-induced late airway response (LAR) and airway eosinophilia, we examined the effect of administration of Ag-primed CD8+ T cells on allergic airway responses, bronchoalveolar lavage (BAL) leukocytes, and mRNA expression for cytokines (IL-4, IL-5, and IFN-gamma) in OVA-sensitized Brown Norway rats. On day 12 postsensitization to OVA, test rats were administered 2 million CD8+ T cells i.p. isolated from either the cervical lymph nodes (LN group; n = 8) or the spleen (Spl group; n = 6) of sensitized donors. On day 14, test rats were challenged with aerosolized OVA. Control rats were administered PBS i.p. on day 12, and challenged with OVA (n = 10) or BSA (n = 6) on day 14. The lung resistance was measured for 8 h after challenge. BAL was performed at 8 h. Cytospin slides of BAL were analyzed for major basic protein by immunostaining and for cytokine mRNA by in situ hybridization. The LAR was significantly less in the LN group (1.8 +/- 0.5 U; p
PubMed ID
10553086 View in PubMed
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Conjugates of ovalbumin and monomethoxypolyethylene glycol abolish late allergic responses and decrease IL-4 and IL-5 mRNA expression in the rat.

https://arctichealth.org/en/permalink/ahliterature9604
Source
Pulm Pharmacol Ther. 2003;16(6):361-9
Publication Type
Article
Date
2003
Author
J-P Lavoie
K. Maghni
R. Taha
X-X Yang
G M Lang
A H Sehon
Q A Hamid
J G Martin
Author Affiliation
Department de Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Sicotte CP5000, St-Hyacinthe, Que., Canada J2S 7C6. jean-pierre.lavoie@umontreal.ca
Source
Pulm Pharmacol Ther. 2003;16(6):361-9
Date
2003
Language
English
Publication Type
Article
Keywords
Animals
Asthma - drug therapy - metabolism - physiopathology
Bronchoalveolar Lavage Fluid - chemistry - cytology
Bronchoconstriction - drug effects
Histamine - analysis
Interferon Type II - biosynthesis - genetics
Interleukin-4 - biosynthesis - genetics
Interleukin-5 - biosynthesis - genetics
Ovalbumin - administration & dosage - immunology - therapeutic use
Polyethylene Glycols - administration & dosage - therapeutic use
RNA, Messenger - biosynthesis
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Abstract
The purpose of this study was to test the therapeutic potential of monomethoxypolyethylene glycol (mPEG) conjugated-allergen using a rodent model of allergic asthma. Previously, this conjugate has been shown to possess the dual capacity of inducing long-term ovalbumin (OA)-specific suppression of the antibody response and inactivating rat mast cells that have been sensitized with murine IgE to OA. Ovalbumin sensitized and challenged Brown Norway rats were studied. Fourteen days after sensitization, a test group of six rats received mPEG-OA solution intratracheally and were challenged 30 min later with aerosolized OA. Another group of seven sensitized rats was similarly challenged with OA 30 min after intratracheal administration of normal saline. A group of six sensitized rats received mPEG-OA solution intratracheally but were challenged with normal saline. Another group of seven sensitized rats received mPEG-BSA solution intratracheally and were challenged 30 min later with aerosolized OA. A final group of five unsensitized rats were neither challenged nor medicated intratracheally. Pulmonary resistance was measured before and for 8 h following inhalation challenge. mPEG-OA treatment had an inhibitory effect on the allergic late airway response, but the early response was not significantly altered. Both mPEG-OA and mPEG-BSA reduced the total cells, eosinophils and neutrophils, in bronchoalveolar lavage and decreased the expression of IL-4, IL-5 and IFN-gamma mRNA. In conclusion, mPEG-OA can prevent the development of allergen-induced late airway responses and reduce airway Th2-type cytokine expression whereas mPEG conjugated to an irrelevant antigen (BSA) is anti-inflammatory but does not affect the late response.
PubMed ID
14580928 View in PubMed
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Effect of dexamethasone on airway inflammation and responsiveness after antigen challenge of the rat.

https://arctichealth.org/en/permalink/ahliterature57718
Source
Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):932-9
Publication Type
Article
Date
Oct-1993
Author
P M Renzi
R. Olivenstein
J G Martin
Author Affiliation
Respiratory Health Network of Centres of Excellence, André Viallet Research Institute, St-Luc Hospital, University of Montreal, Quebec, Canada.
Source
Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):932-9
Date
Oct-1993
Language
English
Publication Type
Article
Keywords
Aerosols
Allergens - immunology
Animals
Antigens - immunology
Bronchitis - drug therapy - etiology - physiopathology
Comparative Study
Dexamethasone - pharmacology - therapeutic use
Immunization
Lung - cytology - drug effects - physiopathology
Lymphocyte Subsets - drug effects
Male
Methacholine Chloride - pharmacology
Rats
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
Respiratory Mechanics - drug effects - physiology
Time Factors
Abstract
The purpose of this study was to examine the effects of dexamethasone on airway responsiveness and lung inflammation of rats at 8 h, 32 h, and 7 d after allergen challenge. Brown-Norway male rats, 7 to 8 wk old, were actively sensitized to ovalbumin (OA) and challenged 14 d later. The rats were divided into a control group (n = 31) and a test group (n = 34) that received dexamethasone (DEXA) (0.3 mg/kg intraperitoneally) 14 h and 2 h before saline or OA challenge. For challenge, rats were anesthetized with pentobarbital and intubated endotracheally. Aerosols of OA (5% wt/vol in saline) were administered for 5 min. Responsiveness to inhaled aerosols of methacholine and the total and differential leukocyte counts in the large airways (generations 0 to 5), small airways, and parenchyma isolated by tissue mincing and digestion were measured at 8 h, 32 h, and 7 d after OA challenge. The cellular influx into the airways and parenchyma was highest at 8 h and decreased progressively over 7 d. DEXA significantly inhibited the cellular influx after allergen challenge. At 8 h, cellular return from the large airways was 3.61 +/- 0.5 x 10(6) (controls) versus 1.0 +/- 0.2 x 10(6) (DEXA), and from the small airways and parenchyma was 31.7 +/- 2.8 x 10(6) (controls) versus 21.9 +/- 2.9 x 10(6) (DEXA) (p
PubMed ID
8214947 View in PubMed
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Effect of interleukin-2 on the airway response to antigen in the rat.

https://arctichealth.org/en/permalink/ahliterature57745
Source
Am Rev Respir Dis. 1992 Jul;146(1):163-9
Publication Type
Article
Date
Jul-1992
Author
P M Renzi
S. Sapienza
S. Waserman
T. Du
R. Olivenstein
N S Wang
J G Martin
Author Affiliation
Meakins Christie Laboratories, Montreal, Quebec, Canada.
Source
Am Rev Respir Dis. 1992 Jul;146(1):163-9
Date
Jul-1992
Language
English
Publication Type
Article
Keywords
Animals
Antigens - administration & dosage
Bronchi - pathology
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - immunology
Bronchoconstriction - physiology
Immunization
Immunoglobulin E - analysis
Immunoglobulin G - analysis
Interleukin-2 - pharmacology - physiology
Leukocyte Count
Lung - pathology
Lymphocytes
Male
Mast Cells - pathology
Methacholine Chloride - diagnostic use
Ovalbumin - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Abstract
To evaluate the hypothesis that lymphocyte stimulation can modify the bronchoconstrictive response to inhalational challenge with an allergen, we administered interleukin-2 (IL-2), an important lymphokine in lymphocyte activation and proliferation, to actively sensitized rats. Brown Norway rats received either human recombinant IL-2 (n = 8) or its vehicle (n = 7) twice a day from the ninth to the fourteenth day after active sensitization to ovalbumin (OA) and were challenged with an aerosol of OA. Lung resistance (RL) during the early response increased to a maximum of 698 +/- 230% and 180 +/- 26% of baseline values in the animals receiving IL-2 and vehicle, respectively (p less than 0.025). The late response was threefold greater in IL-2-treated than in vehicle-treated animals (p = 0.01). IL-2 increased OA-specific IgG levels in the serum, but it did not significantly affect total or specific IgE levels. IL-2 caused an inflammatory infiltrate around the airways with significant increases in eosinophils, lymphocytes, and mast cells prior to antigen challenge. Our results indicate that stimulation of cell-mediated immunity can affect airway responsiveness to antigen.
PubMed ID
1626798 View in PubMed
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IL-3 does not affect the allergic airway responses and leukotriene production after allergen challenge in rats.

https://arctichealth.org/en/permalink/ahliterature15652
Source
Eur Respir J. 1999 May;13(5):970-5
Publication Type
Article
Date
May-1999
Author
T. Du
J G Martin
L J Xu
W S Powell
P M Renzi
Author Affiliation
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Source
Eur Respir J. 1999 May;13(5):970-5
Date
May-1999
Language
English
Publication Type
Article
Keywords
Allergens
Animals
Asthma - immunology
Eosinophils - immunology
Humans
Interleukin-3 - pharmacology
Leukotrienes - biosynthesis
Male
Mast Cells - immunology
Ovalbumin
Rats
Rats, Inbred BN
Recombinant Proteins - pharmacology
Research Support, Non-U.S. Gov't
Abstract
T cell cytokines are important in asthma. Interleukin (IL)-3, an important growth factor for mast cells and eosinophils has been shown to be increased in the airways of asthmatic subjects, but its precise functions are uncertain. The aim of this study was to determine whether recombinant human (rh) IL-3 affected airway responses, inflammation and leukotriene production after antigen challenge in Brown Norway (BN) rats. Having established that rhIL-3 (>12.5 microg subcutaneously b.i.d. for 4 days) caused a doubling of mast cell numbers in the airways of BN rats, sensitized rats were pretreated with rhIL-3 (50 microg) or vehicle subcutaneously b.i.d. for 4 days. Ovalbumin (OA) challenge was performed and the early (EAR), and late (LAR) airway response and the associated biliary leukotriene (LT) excretion measured. The pulmonary cellularity was evaluated by means of lung digestion 8 h after challenge. IL-3 increased the number of eosinophils isolated from the lungs after antigen challenge (0.77+/-0.23 versus 0.38+/-0.12 x 10(6) cells, p=0.03). However, there were no effects on the numbers of neutrophils, lymphocytes and macrophages. Neither the EAR nor the LAR after OA challenge were altered by IL-3. Likewise biliary cysteinyl-LT excretion was similar in IL-3-treated animals and controls after challenge. In conclusion, interleukin-3 caused an increase in the numbers of mast cells and eosinophils around the airways without affecting the magnitude of either early or late airway responses or mediator release after antigen challenge. The present results suggest that airway inflammation can occur in rats without increasing the allergic asthmatic response.
PubMed ID
10414391 View in PubMed
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26 records – page 1 of 3.