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Vol. 50, Issue 4, 515-596, December 1998

Inflammatory Mediators of Asthma: An Update

Peter J. Barnesa, K. Fan Chung and Clive P. Page

Department of Thoracic Medicine (P.J.B., K.F.C), National Heart and Lung Institute, Imperial College, and Department of Pharmacology (C.P.P), Kings College, London, United Kingdom

I. Introduction
    A. Cellular Origin of Mediators
    B. Synthesis and Metabolism
    C. Mediator Receptors
    D. Mediator Effects
    E. Involvement of Mediators in Asthma
    F. Chronic Inflammation
    G. Transcription Factors
    H. Mediator Interactions
II. Amine Mediators
    A. Histamine
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    B. Serotonin (5-Hydroxytryptamine)
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    C. Adenosine
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
III. Lipid-Derived Mediators
    A. Prostanoids
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    B. Leukotrienes
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    C. Platelet-Activating Factor
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    D. Other Lipid Mediators
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
IV. Peptide Mediators
    A. Bradykinin
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    B. Tachykinins
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    C. Calcitonin Gene-Related Peptide
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    D. Endothelins
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    E. Complement
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
V. Small Molecules
    A. Reactive Oxygen Species
        1. Synthesis and metabolism.
        2. Effects on airways.
        3. Role in asthma.
    B. Nitric Oxide
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
VI. Cytokines
    A. General Overview
        1. The cytokine network in chronic inflammation.
        2. Cytokine receptors.
    B. Lymphokines
        1. Interleukin-2.
        2. Interleukin-3.
        3. Interleukin-4.
        4. Interleukin-5.
        5. Interleukin-13.
        6. Interleukin-15.
        7. Interleukin-16.
        8. Interleukin-17.
    C. Proinflammatory Cytokines
        1. Interleukin-1.
        2. Tumor necrosis factor-alpha .
        3. Interleukin-6.
        4. Interleukin-11.
        5. Granulocyte-macrophage colony-stimulating factor.
        6. Stem cell factor.
    D. Inhibitory Cytokines
        1. Interleukin-10.
        2. Interleukin-1 receptor antagonist.
        3. Interferon-gamma .
        4. Interleukin-12.
        5. Interleukin-18.
    E. Growth Factors
        1. Platelet-derived growth factor.
        2. Transforming growth factor-beta .
        3. Fibroblast growth factor.
        4. Epidermal growth factor.
        5. Insulin-like growth factor.
VII. Chemokines
    A. CC Chemokines
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
    B. CXC Chemokines
        1. Synthesis and metabolism.
        2. Receptors.
        3. Effects on airways.
        4. Role in asthma.
VIII. Proteases
    A. Synthesis and Metabolism
    B. Receptors
    C. Effects on Airways
        1. Airway smooth muscle.
        2. Other effects.
    D. Role in Asthma
        1. Release.
        2. Effects of inhibitors.
References

a   Address for correspondence: P. J. Barnes, Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse St., London SW3 6LY, UK. E-mail: p.j.barnes{at}ic.ac.uk.

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Am. J. Respir. Crit. Care Med., August 1, 2002; 166(3): 392 - 396.
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K. Ito, S. Lim, G. Caramori, B. Cosio, K. F. Chung, I. M. Adcock, and P. J. Barnes
A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression
PNAS, June 25, 2002; 99(13): 8921 - 8926.