Allergy is a hypersensitivity disorder characterized by an exaggerated immunologic response to an otherwise innocuous agent, called an allergen. Allergies can be caused by both host (race, gender, hereditary) and environmental factors (pollution, diet, infection).
The increase in allergic diseases industrialized countries over the past decades has been attributed to a decline in infections during childhood, also known as the hygiene hypothesis.
Classification of the Allergic Response
The immunological allergic response is often thought of in terms of the Gell-Coombs classification which states that there are four main types of hypersensitivity.
~ IgE mediated hypersensitivity, seen in food allergy and asthma.
~ Antibody mediated hypersensitivity, seen in transfusion reactions.
~ Immune complex mediated hypersensitivity, seen in arthritis.
~ T-cell mediated (delayed hypersensitivity), seen in dermatitis.
The most common allergic response is Type I. IgE antibodies are produced in response to an allergen in the sensitization phase and antigens are presented to T-helper (Th2) cells. Th2 cell produce cytokines such as IL-3, IL-4 and IL-5 which promote development and survival of other immune cells such as B cells and eosinophils. IgE antibodies then attach to mast cells and basophils and upon a secondary exposure to allergen, antigen-antibody binding will occur at these sites. Crosslinking of IgE on mast cells leads to their degranulation and the release of mediators responsible for the allergic reaction. These mediators increase mucus secretion and promote vascular permeability and smooth muscle contraction. Eosinophils, neutrophils and monocytes are recruited in the late phase and release additional mediators to sustain the allergic response.
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A compound that exhibits anti-inflammatory and immunomodulatory effects by inhibiting lipid mediator and cytokine release from inflammatory cells and interfering with PDGF- and TGF-β1-induced proliferation and migration of vascular medial smooth muscle cells; inhibits endotoxin-induced PGE2 (IC50=1-20 uM), thromboxane B2 (IC50= 10-50 uM), TGF-β1 (IC50=100-200 uM), and IL-8 (IC50=100 uM) formation, but has no effect on TNF-α; also inhibits VEGF-induced angiogenetic activities.
ADX-102 (Reproxalap, NS-2) is a novel small molecule immunomodulator that covalently binds aldehydes including malondialdehyde and 4-hydroxynonenal, which have been shown to mediate inflammatory pain; DX-102 is a promising agent for the treatment of dry eye disease.
A potent, ATP-competitive, reversible, and highly selective inhibitor of Syk tyrosine kinase with Ki of 7.5 nM, displays no inhibitory effect against Btk, Fyn, Itk, Lyn, and Src; inhibits not only degranulation (IC50=5-46 nM) but also lipid mediator and cytokine synthesis in mast cells; suppresses B cell receptor activation and receptors for Fc portion of IgG signaling in eosinophils and monocytes; suppresses antigen-induced passive cutaneous anaphylactic reaction, bronchoconstriction, and bronchial edema at 3 mg/kg in rats; orally bioavailable.
Montelukast sodium (MK0476, MK-0476) is a potent, selective, orally active leukotriene D4 receptor (LTD4) antagonist with Ki of 0.18 nM for guinea pig lung LTD4; shows no significant affinity for leukotriene C4 and leukotriene B4 receptors; Montelukast sodium is a potent and competitive antagonist of leukotriene D4-induced contractions of non-tonal guinea-pig trachea with pA2 of 9.3; antagonizes bronchoconstriction induced in anesthetized guinea pigs by i.v. leukotriene D4, blocksleukotriene D4 induced bronchoconstriction in vivo.
Cortisone acetate (Cortisone 21-acetate) is a synthetic glucocorticoid corticosteroid and corticosteroid ester; the C21 acetate ester of cortisone and acts as a prodrug of cortisone in the body.
Prednisolone is a glucocorticoid with the general properties of the corticosteroids.
Cortisone is a pregnane (21-carbon) steroid hormone, one of the main hormones released by the adrenal gland in response to stress.
AA-861 (Docebenone) is a potent, selective 5-Lipoxygenase (5-LO) inhibitor with IC50 of 0.8 uM; induces cytotoxic and anti-proliferative effects in 5-LO-positive Capan-2 pancreatic cancer cells; also efficiently inhibits biofilms by preventing the formation of amyloid-like fibers.
Loteprednol etabonate is an anti-inflammatory corticosteroid used in optometry and ophthalmology.
Suplatast tosilate is a cytokine inhibitor that attenuates IL-2, IL-5 and IL-13 production and has no effect on IFN-γ production; suppresses IgE production, eosinophil infiltration and histamine release; exhibits antiasthmatic, anti-inflammatory and antifibrotic activity in vivo and is orally active.
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