Inflammatory response late phase

Asthma is an extremely complex condition characterized by variable and reversible airways obstmction combiaed with nonspecific bronchial hypersensitivity (1 3). The cause of asthma, which is not always readily diagnosed (4), remains unknown. Days, if not weeks, ate needed to document the spontaneous reversal of the airways obstmction ia some patients. Asthmatics experience both an immediate hypersensitivity response and a delayed late-phase reaction, each mediated by a different pathway. Chronic asthma has come to be viewed as an inflammatory disease (5). The late-phase reaction plays a key role ia iaduciag and maintaining the inflammatory state which ia turn is thought to iaduce the bronchial hyperresponsiveness (6). The airways obstmction results from both contraction of airways smooth muscle and excessive bronchial edema. Edema, a characteristic of inflammatory states, is accompanied, ia this case, by the formation of a viscous mucus which can completely block the small airways. 

In the late phase response, activated airway cells release inflammatory cytokines and chemokines, recruiting inflammatory cells into the lungs. The late phase response occurs 4 to 6 hours after the initial allergen challenge and results in a less intense bronchoconstriction as well as increased airway hyperresponsiveness and airway inflammation.6... 

Cromolyn and nedocromil are inhaled anti-inflammatory agents that block both the early- and late-phase response. Both agents are considered alternative therapies to inhaled corticosteroids for the treatment of mild persistent asthma however, both are less effective than low doses of inhaled corticosteroids.2,30 The exact mechanism of action of these agents is not understood, but they appear to inhibit mast cell mediator release as well as modulate other inflammatory responses.3... 

From 4 to 8 hours after the initial exposure to an allergen, a late-phase reaction may occur, which is thought to be due to cytokines released primarily by mast cells and thymus-derived helper lymphocytes. This inflammatory response likely is responsible for persistent, chronic symptoms including nasal congestion. 

T-helper cells of atopic people are largely of the Th2 type rather than the Thl that is, they will induce IgE class switching in B-cells (Th2) rather than IgG class switching (Thl). Th2 helper cells synthesise IL-4 and IL-13, which promote class switching, and release IL-5, which attracts eosinophils and other inflammatory cells to the site, producing the late phase of the response. 

Type I hypersensitivity reactions usually occur within minutes to hours of exposure to an antigen in sensitized individuals. The immediate allergic response is initiated 5 to 30 minutes after allergen exposure and resolves in 30 to 60 minutes.This may be followed by the late-phase reaction, which is more severe and of greater duration. The late phase develops 4 to 6 hours after the initial response and may last up to 2 days. Neutrophils, eosinophils, macrophages, lymphocytes, basophils, and mast cells are involved in the late-phase inflammatory reaction, resulting in tissue damage. 

Charlesworth, E.N., Hood, A.F., Soter, N.A., Kagey Sobotka, A., Norman, P.S. and Lichtenstein, L.M. (1989a). Cutaneous late-phase response to allergen. Mediator release and inflammatory cell infiltration. J. Clin. Invest. 83, 1519-1526. 

Late phase inflammatory Response Unknown Mechanism OF Plasma leakage... 

It is uncertain which vessels leak in the late phase response. Although venules are labelled with the tracer Monastral blue in a dog model of allergen-induced late phase response (Ohrui et al., 1992), no vessels are labelled in the late phase response evoked in guinea-pig airways by PAF (O Donnell et al., 1990). It is unclear whether this diflference is due to differences in the animal models or to limitations of the methods used to identify the leaky vessels. One reason for considering that the late phase leak may not be just a longer version of the early response is evidence that prolonged inflammatory stimuli... 

Leukotriene receptor antagonists are a relatively new class of drugs that directly bind to leukotriene receptors in the lung preventing the inflammatory actions of leukotrienes particularly in the late phase of asthma. They are used in cases of asthma where there is a poor response to bronchodilators alone. 

Corticosteroids are anti-inflammatory drugs that can be used in asthma to reduce airway hyper-responsiveness and to decrease bronchial oedema and mucus secretion. They are effective in the late phase reaction and reduce the intensity of allergic reactions. They are used in emergency treatment of severe acute attacks, for the treatment of mild to moderate attacks and prophylactically to prevent attacks. Corticosteroids can be useful in reducing acute exacerbations of chronic bronchitis. 

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