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Article

Mediators of Chronic Obstructive Pulmonary Disease

National Heart and Lung Institute, Imperial College, London, United Kingdom

Abstract

I. Introduction

II. Chronic Obstructive Pulmonary Disease as an Inflammatory Disease

A. What is Chronic Obstructive Pulmonary Disease?

B. Differences from Asthma

C. Inflammatory Cells

III. Lipid Mediators

A. Prostanoids

B. Leukotrienes

C. Platelet-Activating Factor

IV. Reactive Oxygen Species

A. Formation

B. Antioxidants

C. Evidence for Increased Oxidative Stress

D. Effects on Airway Function

E. Effects of Antioxidants

V. Nitric Oxide

A. Formation

B. Inhibition

VI. Peptide Mediators

A. Endothelins

B. Bradykinin

C. Tachykinins

D. Complement Fragments

VII. Chemokines

A. Interleukin-8

B. Growth-Related Oncogene-{alpha}

C. Epithelial Cell-Derived Neutrophil-Activating Peptide-78

D. CXC3 Chemokines

E. Monocyte Chemoattractant Protein-1

F. Macrophage Inflammatory Protein

G. Eosinophil-Selective Chemokines

H. Lymphocyte-Selective Chemokines

I. Dendritic Cell-Selective Chemokines

J. CX3C Chemokines

VIII. Cytokines

A. Tumor Necrosis Factor-{alpha}

B. Interleukin-1{beta}

C. Interleukin-6

D. Interleukin-9

E. Granulocyte-Macrophage Colony Stimulating Factor

F. Interleukin-10

G. Interleukin-12

H. Interleukin-13

I. Interleukin-17

J. Interferon-{gamma}

IX. Growth Factors

A. Transforming Growth Factors

B. Epidermal Growth Factor

C. Vascular-Endothelial Growth Factor

D. Fibroblast Growth Factors

X. Proteases

A. Neutrophil Elastase

B. Other Serine Proteases

C. Cysteine Proteases

D. Matrix Metalloproteinases

E. Antiproteases

XI. Conclusions

Chronic obstructive pulmonary disease (COPD) is a major and increasing global health problem that is now a leading cause of death. COPD is associated with a chronic inflammatory response, predominantly in small airways and lung parenchyma, which is characterized by increased numbers of macrophages, neutrophils, and T lymphocytes. The inflammatory mediators involved in COPD have not been clearly defined, in contrast to asthma, but it is now apparent that many lipid mediators, inflammatory peptides, reactive oxygen and nitrogen species, chemokines, cytokines, and growth factors are involved in orchestrating the complex inflammatory process that results in small airway fibrosis and alveolar destruction. Many proteases are also involved in the inflammatory process and are responsible for the destruction of elastin fibers in the lung parenchyma, which is the hallmark of emphysema. The identification of inflammatory mediators and understanding their interactions is important for the development of anti-inflammatory treatments for this important disease.

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