Skip header and navigation

Refine By

22 records – page 1 of 3.

Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature57604
Source
Immunology. 1997 Jun;91(2):176-85
Publication Type
Article
Date
Jun-1997
Author
A. Haczku
P. Macary
T J Huang
H. Tsukagoshi
P J Barnes
A B Kay
D M Kemeny
K F Chung
R. Moqbel
Author Affiliation
Department of Allergy and Clinical Immunology, Guy's Hospital, London, UK.
Source
Immunology. 1997 Jun;91(2):176-85
Date
Jun-1997
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Bronchial Hyperreactivity - immunology
Bronchoalveolar Lavage Fluid - immunology
CD4-Positive T-Lymphocytes - immunology - transplantation
CD8-Positive T-Lymphocytes - immunology - transplantation
Cell Culture Techniques
Cell Division - immunology
Eosinophils - immunology
Leukocyte Count
Lymphocyte Transfusion
Male
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Spleen - immunology
Abstract
Following allergen exposure, sensitized Brown-Norway rats develop airway hyperresponsiveness (AHR) and eosinophilic inflammation together with an increase in activated T cells (CD25+) in the airways. We tested the hypothesis that CD4+ T cells are involved directly in the acquisition of AHR. Spleen T cells from animals that were injected intraperitoneally on three consecutive days with ovalbumin/Al(OH)3, showed a dose-dependent proliferative response in vitro to ovalbumin, but not to bovine serum albumin, as measured by [3H]thymidine uptake. For total T-cell transfer, spleen cells obtained from donor rats 4 days after sensitization were depleted of adherent cells by a nylon wool column separation. CD4+ and CD8+ T cells were purified by immunomagnetic beads cell separation. Recipient naive rats were injected intravenously with 50 x 10(6) total T cells, 20 x 10(6) and 5 x 10(6) CD4+ cells, and 5 x 10(6) CD8+ cells, and were exposed to ovalbumin aerosol 24 hr afterwards. After a further 24 hr, airway responsiveness to acetylcholine (ACh) was measured and provocative concentration (PC) values PC100, PC200 and PC300) (the ACh concentration needed to achieve 100, 200 and 300% increase in lung resistance above baseline) were calculated. Airway responsiveness was significantly increased in recipients of sensitized total T cells compared with recipients of cells from saline-injected donor rats (P
PubMed ID
9227314 View in PubMed
Less detail

Airway hyperresponsiveness, elevation of serum-specific IgE and activation of T cells following allergen exposure in sensitized Brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature15906
Source
Immunology. 1995 Aug;85(4):598-603
Publication Type
Article
Date
Aug-1995
Author
A. Haczku
K F Chung
J. Sun
P J Barnes
A B Kay
R. Moqbel
Author Affiliation
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, UK.
Source
Immunology. 1995 Aug;85(4):598-603
Date
Aug-1995
Language
English
Publication Type
Article
Keywords
Allergens - immunology
Animals
Bronchial Hyperreactivity - immunology
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - immunology
Female
Immunoglobulin E - blood
Lymphocyte Activation - immunology
Ovalbumin - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
T-Lymphocyte Subsets - immunology
Abstract
T lymphocytes may play a regulatory role in the development of allergic airway hyperresponsiveness (AHR). We have studied the relationship between airway responsiveness and a number of immunological changes in Brown-Norway rats sensitized intraperitoneally and repeatedly exposed to ovalbumin (OVA) aerosol. Acetylcholine provocation concentration (PC)150 (the concentration of acetylcholine causing a 150% increase of base-line lung resistance) was measured and peripheral blood and bronchoalveolar lavage (BAL) cells were collected 18-24hr after the final exposure. Total and OVA-specific IgE in serum was measured by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells were analysed by flow cytometry after labelling with monoclonal antibodies against CD2 (pan T-cell marker), CD4, CD8 (T-cell subsets) or CD25 (interleukin-2 receptor). There were significant differences in PC150 (P
PubMed ID
7558155 View in PubMed
Less detail

Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma.

https://arctichealth.org/en/permalink/ahliterature15527
Source
J Immunol. 2001 Jan 1;166(1):207-17
Publication Type
Article
Date
Jan-1-2001
Author
T J Huang
P A MacAry
P. Eynott
A. Moussavi
K C Daniel
P W Askenase
D M Kemeny
K F Chung
Author Affiliation
Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Source
J Immunol. 2001 Jan 1;166(1):207-17
Date
Jan-1-2001
Language
English
Publication Type
Article
Keywords
Administration, Inhalation
Adoptive Transfer
Allergens - administration & dosage - immunology
Animals
Antibodies, Monoclonal - administration & dosage
Bronchial Hyperreactivity - immunology - pathology - prevention & control
Bronchoalveolar Lavage Fluid - immunology
Cell Line
Epitopes, T-Lymphocyte - administration & dosage - immunology
Inflammation - immunology - pathology - prevention & control
Injections, Intravenous
Interferon Type II - immunology - physiology
Interleukin-4 - antagonists & inhibitors - genetics
Lung - cytology - immunology
Male
Ovalbumin - administration & dosage - immunology
Pulmonary Eosinophilia - immunology - pathology - prevention & control
RNA, Messenger - antagonists & inhibitors
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Th1 Cells - immunology - transplantation
Th2 Cells - immunology - transplantation
Abstract
Th2 T cell immune-driven inflammation plays an important role in allergic asthma. We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia. OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge. Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA. Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 cells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma. Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.
PubMed ID
11123294 View in PubMed
Less detail

Alveolar macrophages of allergic resistant and susceptible strains of rats show distinct cytokine profiles.

https://arctichealth.org/en/permalink/ahliterature15450
Source
Clin Exp Immunol. 2001 Oct;126(1):9-15
Publication Type
Article
Date
Oct-2001
Author
J. Sirois
E Y Bissonnette
Author Affiliation
Département de médecine, Centre de recherche, Hôpital Laval, Institut universitaire de cardiologie et de pneumologie de l'Université Laval, Sainte-Foy, Canada.
Source
Clin Exp Immunol. 2001 Oct;126(1):9-15
Date
Oct-2001
Language
English
Publication Type
Article
Keywords
Administration, Inhalation
Animals
Asthma - immunology
Bronchoalveolar Lavage Fluid - immunology
Cells, Cultured
Comparative Study
Cytokines - biosynthesis - genetics
Hypersensitivity, Immediate - immunology
Interleukins - biosynthesis - genetics
Macrophage Inflammatory Protein-1 - biosynthesis - genetics
Macrophages, Alveolar - immunology
Nitric Oxide - biosynthesis
Ovalbumin - administration & dosage - immunology
RNA, Messenger - biosynthesis
Rats
Rats, Sprague-Dawley
Research Support, Non-U.S. Gov't
Th1 Cells - immunology
Th2 Cells - immunology
Tumor Necrosis Factor-alpha - biosynthesis - genetics
Abstract
Brown Norway rats are widely used as a model of asthma, whereas Sprague Dawley rats do not develop allergic reactions under the same conditions. Given the importance of alveolar macrophages (AM) in down-regulating cellular immune responses in the lung, we postulated that the different susceptibilities in the development of airway allergic reactions in these rat strains may be related to functional differences in their AM. We investigated the production of important mediators in asthma, namely tumour necrosis factor (TNF), interleukin-10 (IL-10), IL-12, IL-13, nitric oxide (NO) and macrophage inflammatory protein-1alpha (MIP-1alpha), by AM of unsensitized Sprague Dawley and Brown Norway rats. AM were purified by adherence and stimulated with OX8 (anti-CD8 antibody) or LPS. OX8 stimulation significantly increased the release of TNF, IL-10 and NO in both strains of rats, whereas MIP-1alpha and IL-12 release were increased in Brown Norway rats only. Interestingly, stimulated AM from Sprague Dawley rats released significantly more TNF and less IL-10, IL-12, IL-13, MIP-1alpha and NO compared with AM from Brown Norway rats. These differences were also observed at the mRNA level, except for TNF. Thus, AM from Brown Norway and Sprague Dawley rats are functionally different. Furthermore, LPS- and OX8-stimulated AM from Brown Norway rats produce more Th2 type cytokines (IL-10 and IL-13) than AM from Sprague Dawley rats, suggesting that these cells may play an important role in creating a cytokine milieu that may favour the development of allergic reactions.
PubMed ID
11678894 View in PubMed
Less detail

CD8+ alphabeta T cells can mediate late airway responses and airway eosinophilia in rats.

https://arctichealth.org/en/permalink/ahliterature57391
Source
J Allergy Clin Immunol. 2004 Dec;114(6):1345-52
Publication Type
Article
Date
Dec-2004
Author
Susumu Isogai
Rame Taha
Meiyo Tamaoka
Yasuyuki Yoshizawa
Qutayba Hamid
James G Martin
Author Affiliation
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Source
J Allergy Clin Immunol. 2004 Dec;114(6):1345-52
Date
Dec-2004
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Bronchoalveolar Lavage Fluid - immunology
CD8-Positive T-Lymphocytes - immunology
Cytokines - biosynthesis
Eosinophilia - etiology
Lung Diseases - etiology
Male
Ovalbumin - immunology
Rats
Rats, Inbred BN
Receptors, Antigen, T-Cell, alpha-beta - analysis
Research Support, Non-U.S. Gov't
Abstract
BACKGROUND: The function of CD8+ T-cell subsets in mediating late allergic responses is incompletely understood. OBJECTIVE: We sought to test the hypothesis that CD8+ alphabeta T cells are proinflammatory in the airways in vivo by using a well-characterized animal model and the technique of adoptive transfer. METHODS: Brown Norway rats were administered CD8 + alphabeta T cells (10 6 ) intraperitoneally purified from lymph node cells of either naive or ovalbumin (OVA)-sensitized rats and were challenged with aerosolized OVA 2 days later. Control rats were sensitized to 100 mug of OVA in Al(OH) 3 subcutaneously or sham sensitized to saline and were OVA challenged 2 weeks later. RESULTS: The OVA-sensitized and OVA-challenged group and the recipients of OVA-primed CD8+ alphabeta T cells had significant late airway responses calculated from lung resistance measured for an 8-hour period after challenge compared with the naive CD8 + alphabeta T cell-transferred group and the sham-sensitized control group. The number of eosinophils in bronchoalveolar lavage fluid increased in the OVA-sensitized group and the OVA-primed CD8+ alphabeta T-cell recipients compared with numbers in the naive CD8+ alphabeta T-cell recipients and the sham-sensitized control group. IL-4 and IL-5 cytokine mRNA expression in bronchoalveolar lavage fluid increased in the OVA-sensitized group and the OVA-primed CD8+ alphabeta T-cell recipients compared with that in the sham-sensitized group. CONCLUSION: We conclude that antigen-primed CD8 + alphabeta T cells might have a proinflammatory role in allergen-driven airway responses in the rat.
PubMed ID
15577833 View in PubMed
Less detail

CD26 (dipeptidyl-peptidase IV)-dependent recruitment of T cells in a rat asthma model.

https://arctichealth.org/en/permalink/ahliterature15108
Source
Clin Exp Immunol. 2005 Jan;139(1):17-24
Publication Type
Article
Date
Jan-2005
Author
C. Kruschinski
T. Skripuletz
S. Bedoui
T. Tschernig
R. Pabst
C. Nassenstein
A. Braun
S. von Hörsten
Author Affiliation
Department of Functional and Applied Anatomy, Medical School of Hannover, Hannover, Germany.
Source
Clin Exp Immunol. 2005 Jan;139(1):17-24
Date
Jan-2005
Language
English
Publication Type
Article
Keywords
Animals
Antigens, CD26 - immunology
Asthma - blood - immunology
Bronchoalveolar Lavage Fluid - immunology
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes - immunology
Comparative Study
Disease Models, Animal
Eosinophils - immunology
Immunoglobulin E - blood
Lymphocyte Count
Lymphocytes - immunology
Ovalbumin - immunology
Rats
Rats, Inbred BN
Rats, Inbred F344
Rats, Inbred Lew
Receptors, Antigen, T-Cell - immunology
Research Support, Non-U.S. Gov't
T-Lymphocytes - immunology
Abstract
CD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26- T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production.
Notes
Erratum In: Clin Exp Immunol. 2005 Apr;140(1):192
PubMed ID
15606609 View in PubMed
Less detail

Effect of an inhibitor of Jun N-terminal protein kinase, SP600125, in single allergen challenge in sensitized rats.

https://arctichealth.org/en/permalink/ahliterature15159
Source
Immunology. 2004 Jul;112(3):446-53
Publication Type
Article
Date
Jul-2004
Author
Paul R Eynott
Li Xu
Brydon L Bennett
Alistair Noble
Sum-Yee Leung
Puneeta Nath
David A Groneberg
Ian M Adcock
K Fan Chung
Author Affiliation
Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Source
Immunology. 2004 Jul;112(3):446-53
Date
Jul-2004
Language
English
Publication Type
Article
Keywords
Allergens - pharmacology
Animals
Anthracenes - pharmacology
Asthma - immunology
Bronchoalveolar Lavage Fluid - immunology
Cell Count
Cytokines - immunology
Enzyme Activation
Eosinophils - immunology
JNK Mitogen-Activated Protein Kinases
Leukocyte Count
Leukocytes, Mononuclear - immunology
Lung - enzymology - immunology
MAP Kinase Kinase 4
Macrophages - immunology
Male
Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors - metabolism
Mitogen-Activated Protein Kinases - metabolism
Models, Animal
Neutrophils - immunology
Ovalbumin
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
p38 Mitogen-Activated Protein Kinases
Abstract
Jun N-terminal kinase (JNK) has been implicated in the pathogenesis of inflammatory diseases including asthma. We examined the effect of SP600125 (anthra [1,9-cd] pyrazol-6 (2H)-one), a novel inhibitor of JNK in a model of asthma. Brown-Norway rats were sensitized to ovalbumin and treated with SP600125 intraperitoneally (90 mg/kg in total). SP600125 inhibited allergen-induced, increased activity of phosphorylated c-jun but not of phosphorylated-MAPKAPK2, indicative of activation of p38 MAPK, in the lung. SP600125 inhibited macrophage (P
PubMed ID
15196213 View in PubMed
Less detail

Effect of CD8+ T-cell depletion on bronchial hyper-responsiveness and inflammation in sensitized and allergen-exposed Brown-Norway rats.

https://arctichealth.org/en/permalink/ahliterature15670
Source
Immunology. 1999 Mar;96(3):416-23
Publication Type
Article
Date
Mar-1999
Author
T J Huang
P A MacAry
D M Kemeny
K F Chung
Author Affiliation
Thoracic Medicine, Chang Gung Memorial Hospital, Keelung Branch, Taiwan, China; Thoracic Medicine, National Heart & Lung Institute, Imperial College School of Medicine, London, UK.
Source
Immunology. 1999 Mar;96(3):416-23
Date
Mar-1999
Language
English
Publication Type
Article
Keywords
Acetylcholine - immunology
Allergens - immunology
Animals
Antibodies, Monoclonal - immunology
Asthma - immunology - physiopathology
Blotting, Southern
Bronchial Hyperreactivity - immunology
Bronchoalveolar Lavage Fluid - immunology
CD8-Positive T-Lymphocytes - immunology
Cytokines - biosynthesis
Immunoenzyme Techniques
Lung - immunology
Lymphocyte Count
Male
Mice
Ovalbumin - immunology
Rats
Rats, Inbred BN
Reverse Transcriptase Polymerase Chain Reaction
Vasodilator Agents - immunology
Abstract
We examined the role of CD8+ T cells in a Brown-Norway rat model of asthma, using a monoclonal antibody to deplete CD8+ T cells. Ovalbumin (OA)-sensitized animals were given anti-CD8 antibody (0.5 mg/rat) intravenously 1 week prior to exposure to 1% OA aerosol and were studied 18-24 hr after aerosol exposure. Following administration of anti-CD8 antibody, CD8+ cells were reduced to
PubMed ID
10233723 View in PubMed
Less detail

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
Less detail

Elevated CXCL10 (IP-10) in bronchoalveolar lavage fluid is associated with acute cellular rejection after human lung transplantation.

https://arctichealth.org/en/permalink/ahliterature107338
Source
Transplantation. 2014 Jan 15;97(1):90-7
Publication Type
Article
Date
Jan-15-2014
Author
Shahid Husain
Mariangela R Resende
Nimerta Rajwans
Ricardo Zamel
Joseph M Pilewski
Maria M Crespo
Lianne G Singer
Kenneth R McCurry
Jay K Kolls
Shaf Keshavjee
W Conrad Liles
Author Affiliation
1 Division of Infectious Diseases, Department of Medicine, Multi-Organ Transplant Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada. 2 Division of Infectious Diseases, Department of Medicine, Toronto General Research Institute, McLaughlin-Rotman Centre for Global Health, McLaughlin Centre for Molecular Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada. 3 The Toronto Lung Transplant Program, McEwen Centre for Regenerative Medicine, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada. 4 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA. 5 Division of Respirology, Department of Medicine, The Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada. 6 Department of Cardiothoracic Surgery, Cleveland Clinic, Cleveland, OH. 7 Departments of Pediatrics and Immunology, University of Pittsburgh, Pittsburgh, PA. 8 Department of Medicine, University of Washington, Seattle, WA. 9 Address correspondence to: Shahid Husain, M.D., M.S., Division of Infectious Diseases, Department of Medicine, Multi-Organ Transplant Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Source
Transplantation. 2014 Jan 15;97(1):90-7
Date
Jan-15-2014
Language
English
Publication Type
Article
Keywords
Acute Disease
Biological Markers - analysis
Bronchoalveolar Lavage Fluid - immunology
Case-Control Studies
Chemokine CXCL10 - analysis
Female
Graft Rejection - immunology
Humans
Immunity, Cellular
Linear Models
Lung Transplantation - adverse effects
Male
Middle Aged
Odds Ratio
Ontario
Pennsylvania
Prospective Studies
Risk factors
Up-Regulation
Abstract
CXCL10 (IP-10) is a potent chemoattractant for T cells that has been postulated to play a role in infection and acute cellular rejection (ACR) in animal models. We measured CXCL10 (IP-10) (and other cytokines previously implicated in the pathogenesis of ACR) in the bronchoalveolar lavage (BAL) of lung transplant recipients (LTRs) to determine the association between CXCL10 (IP-10) and ACR in LTRs.
In a prospective study of 85 LTRs, expression of cytokines (tumor necrosis factor, interferon-?, interleukin [IL]-6, IL-8, IL-15, IL-16, IL-17, CXCL10 [IP-10], and MCP-1 [CCL2]) in BAL samples (n=233) from patients with episodes of ACR (n=44), infection ("Infect"; n=25), concomitant "Infect+ACR" (n=10), and "No Infect and No ACR" (n=154) were analyzed.
The levels of both CXCL10 (IP-10) and IL-16 were significantly increased in histologically proven ACR compared with the "No Infect and No ACR" group (CXCL10 [IP-10]: 107.0 vs. 31.9 pg/mL [P=0.001] and IL-16: 472.1 vs. 283.01 pg/mL [P=0.01]). However, in a linear mixed-effects model, significant association was found only between CXCL10 (IP-10) and ACR. A one-log increase of CXCL10 (IP-10) was associated with a 40% higher risk of ACR (odds ratio, 1.4; 95% confidence interval, 1.12-1.84).
Higher values of CXCL10 (IP-10) in BAL fluid are associated with ACR in LTRs, suggesting a potential mechanistic role in the pathogenesis of ACR in LTRs. These results suggest that therapeutic strategies to inhibit CXCL10 (IP-10) and or its cognate receptor, CXCR3, warrant investigation to prevent and/or treat ACR in clinical lung transplantation.
PubMed ID
24025324 View in PubMed
Less detail

22 records – page 1 of 3.