Journal of Allergy and Clinical Immunology
Inflammation in asthma: The cornerstone of the disease and target of therapy☆,☆☆,★
Section snippets
ACTIVATORS OF ASTHMA
Many factors influence the severity of asthma. Recently, activators of asthma have been divided into 2 general classes: inducers (causes) and provokers (exacerbations) (Fig 1).8Inducers are factors that not only increase the intensity of asthma or its severity but also influence the level of underlying inflammation. As a consequence, inducers increase asthma severity, and these effects can persist long after initial exposure to a causative agent. More specifically,
MAST CELLS
Mast cells develop from bone marrow progenitor cells and are found in increased numbers in the airways of patients with asthma.14 These cells have unique characteristics, which include high-affinity receptors for IgE (Table I).
Activation—IgE dependent Mediators Spasmogens Inducers of inflammation: Proteases Cytokines Regulation by anti-inflammatory therapy Corticosteroids: ↓ Growth and development Cromones: ? Modification of mediator release Theophylline: Perhaps none Leukotriene modifiers:
EOSINOPHILS
Antigen inhalation causes eosinophil recruitment to the lung in asthma, and these cells are the principal effector cells in the resulting inflammatory process (Table II).
Principal effector cells in the inflammatory process Mediators Cysteinyl leukotrienes Granular proteins Cytokines Mechanisms of participation Migration and upregulation Effects are noted in the mucosa and epithelium Regulation by anti-inflammatory therapy Corticosteroids: Induce apoptosis Suppress lymphocyte generation of IL-5
LYMPHOCYTES
Activated lymphocytes are an important component of airway inflammation in asthma (Table III).
T
H2 , T helper cell 2.Source of inflammatory mediators TH2 -like cytokine profile Memory/long-lived cell Regulation by anti-inflammatory therapy Corticosteroids: Inhibit cytokine production Cromones: Effect not established Theophylline: ? Effect on lymphocyte subpopulations Leukotriene modifiers: Effect not established
EPITHELIAL CELLS
Epithelial cells are another source of proinflammatory mediators in asthma including eicosanoids, cytokines, chemokines, and nitric oxide (Table IV).72, 73
Source of mediators Eicosanoids Cytokines Chemokines Nitric oxide Regulation by anti-inflammatory therapy Corticosteroids: Inhibit transcription of cytokines (IL-8, TNF-α, RANTES, GM-CSF) Inhibit inducible nitric oxide synthesis Cromones: Effect not established Theophylline: Effect not established Leukotriene modifiers: Effect not
SUMMARY
Airway inflammation is an important feature of asthma. The intensity of inflammation is influenced by various inducers and provokers of asthma. Furthermore treatment with anti-inflammatory medications modifies the pattern of inflammation in asthma and the generation or expression of proinflammatory mediators. Studies with anti-inflammatory medications have provided valuable insight into mechanisms of asthma and the actions of drugs used in the management of this disease. Although these
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From the Department of Medicine, University of Wisconsin–Madison.
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Reprint requests: William W. Busse, MD, University of Wisconsin–Madison, Department of Medicine, J5/220 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-2454.
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