IL-6 Inhibitor Induction in Coculture Of Bronchial Epithelial Cells and Eosinophils

IL-6 Inhibitor
Eosinophil infiltration of the mucosa is a feature of asthmatic airways. Their adhesion to bronchial epithelial cells has been proposed to lead to the generation of inflammation mediators which may contribute to asthma pathology. Bronchial epithelial cells (BEAS-2B cell line) and peripheral blood eosinophils were cultured alone or in combination and the production of an inflammatory cytokine, IL-6, was measured. IL-6 was produced principally by epithelial cells and the production was enhanced more than 10-fold in the presence of eosinophils. Significant augmentation of epithelial IL-6 production persisted even when eosinophils were fixed with paraformaldehyde. The eosinophil-induced IL-6 production was extensively inhibited by inhibitors of p38 mitogen-activated protein (MAP) kinase or nuclear factor ??B (NF??B). (more…)

Aspirin-Induced Asthma Treatment with Antileukotrienes

Aspirin Asthma
The prevalence of aspirin-sensitive asthma is uncertain although it may exist in up to 20% of all asthmatics patients. The characteristic features include profound bronchoconstriction asthma following aspirin ingestion, rhinosinusitis, nasal polyps, and abdominal cramps. Aspirin and nonsteroidal antiinflammatory drugs selectively inhibit COX-1, which in turn shunts arachidonic acid down the 5-lipoxygenase activating protein pathway, causing overproduction of cysteinyl leukotrienes. As a consequence, elevated levels of cysteinyl leukotrienes can be found in bronchial asthma and nasal aspirates, and in urine following aspirin challenge. (more…)

Antileukotrienes in Acute Asthma: Zafirlukast, Montelukast, Leukotriene Receptor Antagonists

Leukotriene Receptor Antagonists
Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bronchoconstrictor stimuli in the laboratory. This in turn indicates that they may have a role in the pathogenesis of acute episodes of bronchoconstriction. Although antileukotrienes are not currently advocated in the management of acute asthma, there are data to suggest that they might be of some potential benefit. Prior treatment with montelukast asthma has been shown in several studies to significantly shorten the time taken to recover (in terms of FEV 1 ) following exposure to a bronchoconstrictor stimulus. (more…)

Allergen-Specific Immunotherapy Mechanisms & The Involvement Of Treg Cells

allergen specific immunotherapy
Allergen-specific immunotherapy is highly effective in the treatment of IgE-mediated allergy diseases such as rhinitis, conjunctivitis, asthma, and venom allergy hypersensitivity. It is the only treatment that leads to lifelong tolerance against previously disease-causing allergens due to restoration of the normal immunity. (more…)

Cysteinyl Leukotriene Biosynthesis

cysteinyl leukotrienes
The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are lipid mediators produced from an arachidonic acid precursor following a series of enzymatic steps. Arachidonic acid is firstly released from the phospholipid bilayer by phospholipase A 2 and may be metabolized by either the cyclooxygenase (COX) or 5-lipoxygenase pathway. Once the unstable precursor LTA 4 has been produced, it may be converted in neutrophils or monocytes to the noncysteinyl LTB 4 by LTA 4 hydrolase. In mast cells, eosinophils, macrophages, and basophils, LTA 4 may alternatively be converted into LTC 4 by LTC 4 synthase and subsequently into LTD 4 and LTE 4. (more…)

Antileukotriene Drugs for Airway Hyperresponsiveness & Asthma Treatment

antileukotriene
A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which results in the episodic airflow obstruction characteristic of asthma. As a consequence, modulation of the underlying disease process with antii-nflammatory agents is firmly established as being the cornerstone of successful management. Inhaled corticosteroids are the most potent antiinflammatory agents available and satisfactorily suppress underlying airway inflammation in most individuals. (more…)

Mononuclear Phagocytes: The Monocyte Macrophage System

Nearly all tissues, organs, and serosal cavities harbor a population of resident phagocytes. Most contain only a diffuse scattering of individual phagocytic cells that remain inconspicuous under normal conditions and are very similar to one another in appearance and function. In some tissues, however, phagocytes are especially abundant or have distinctive morphologic features and are known by specific names. Examples include the Kupffer cells that line sinusoids of the liver (and account for nearly 10% of total liver mass), osteoclasts in bone, or microglial cells of the brain (Table bellow). (more…)

Microscopic Blood Vessels Dilatation and Increased Permeability

blood vessels
The response to injury usually begins with dilatation of small blood vessels in and around the injured site (figure bellow). This response (called vasodilatation) results from relaxation of smooth muscle in the vascular walls. It can begin within seconds after an acute injury or develop over hours or days of low-grade irritation or infection. Vasodilatation initially results in increased blood flow through arterioles, capillaries, and venules of the affected region, leading to redness (erythema) and warmth. As the vessels dilate, endothelial cells lining some of the vessels actively retract away from one another to create temporary, microscopic gaps in the endothelial lining. Endothelial retraction occurs only in the smallest venules (often called postcapillary venules), which are thin-walled vessels with lumenal diameters of 20 - 60 µm. (more…)

Acute-Phase Response: The Innate Immune System

acute phase response
With the exception of complement protein C3, most soluble mediators of innate immunity are found in relatively small amounts in the serum under normal conditions. The concentrations of several of these proteins, however, can increase as much as 1000-fold during serious infections or other crises, as part of a coordinated protective reaction called the acute-phase response. In this response, the liver temporarily increases its synthesis of more than 30 different serum proteins, often called acute-phase proteins (Table bellow). Many of these, such as complement factors C3 and B, MBL, LBP, C-reactive protein, and serum amyloid protein P, participate in antimicrobial defense. (more…)

Leukocyte Chemotactic Factors

Once it is tethered onto the venule wall, the neutrophil or other leukocyte comes into contact with a wide variety of inflammatory mediators that may either be expressed by the activated endothelium or simply diffuse into the blood from the injured tissue. Among these mediators are a diverse subset of intermediaries known as leukocyte chemotactic factors which bind to receptors on the leukocyte surface and trigger the second, activation phase of margination. (more…)

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