Inflammation mechanisms

Huber, W. (1980). Future trends in free radical studies. In Inflammation Mechanisms and Treatment (eds. D.A. Willoughby and J.A. Giroud) pp. 27-41. MTP Press, Lancaster. 

The acute inflammatory response (see Table 14.1) leads to inflammation, redness, swelling, heat and pain, due to extravasation (leakage) of plasma and infiltration of leukocytes into the site of inflammation. Mechanisms that allow cells and proteins to gain access to damaged or infected extravascular sites include ... 

Polyphenols in blackcurrant fruit, mainly anthocyanins, have been shown experimentally to inhibit inflammation mechanisms under study for the origin of several diseases, including cancer, chronic arthritis, and diabetes. Similarly, studies using an enriched fraction of simple sugars from blackcurrants, such as arabinose and galactose, fed to mice with cancer demonstrated slower growth of the tumors. 

D. Brenn, F. Richter, H. Schaible, Sensitization of unmyelinated sensory fibers o the joint nerve to mechanical stimuli by interleukin-6 in the rat An inflammator mechanism of joint pain. Arthritis Rheum., 56 (1), 351-359,2007. http //dx.doi.org/10.1002/art.22282. K.J. Bar, et al. Changes in the effect of spinal prostaglandin E2 during inflammation Prostaglandin E (EP1-EP4) receptors in spinal nociceptive processing of input from the normal or inflamed knee joint, J. Neuroscl, 24 (3), 642-651, 2004. http //dx.doi.org/ 10.1523/JNEUROSCI.0882-03.2004. 

The number of known cytokines, as well as the diversity of biological functions, have led to a very complex and often confusing picture of the immunologic and nonimmunologic processes involved. The role of cytokiaes in local or systemic homeostatic mechanisms related to physiological functions may be utilized therapeutically for treatment of cancer and a variety of other diseases (2). Pharmaceutical research and development efforts surrounding lL-1 are typical examples of the cytokine inhibition approach to chronic inflammation research (2). 

Primary irritants cause inflammation. Inflammation is one of the body s defence mechanisms. It is the reaction of a tissue to harm which is insufficient to kill the tissue and is typified by... 

The particle size is the most important factor that contributes to the clearance of particles. For particles deposited in the anterior parts of the nose, wiping and blowing are important mechanisms whereas particles on the other areas of the nose are removed with mucus. The cilia move the mucus toward the glottis where the mucus and the particles are swallowed. In the tracheobronchial area, the mucus covering the tracheobronchial tree is moved upward by the cilia beating under the mucus. This mucociliary escalator transports deposited particles and particle-filled macrophages to the pharynx, where they are also swallowed. Mucociliary clearance is rapid in healthy adults and is complete within one to two days for particles in the lower airways. Infection and inflammation due to irritation or allergic reaction can markedly impair this form of clearance. 

The drug SC-558 acts by a fourth mechanism, specifically inhibiting COX-2. It is a weak competitive inhibitor of COX-1 but inhibits COX-2 in a slow, time-dependent process. Specific COX-2 inhibitors will likely be the drugs of the future because they selectively block the inflammation mediated by COX-2, without the potential for stomach lesions and renal toxicity that arise from COX-1 inhibition. 

Aspirin and other NSAIDs function by blocking the cyclooxygenase (COX) enzymes that carry out the body s synthesis of prostaglandins (Sections 7.11 and 27.4). There are two forms of the enzyme, COX-1, which carries out the normal physiological production of prostaglandins, and COX-2, which mediates the body s response to arthritis and other inflammatory conditions. Unfortunately, both COX-1 and COX-2 enzymes are blocked by aspirin, ibuprofen, and other NSAIDs, thereby shutting down not only tire response to inflammation but also various protective functions, including the control mechanism for production of acid in the stomach. 

Luster, A. D. (1998). Mechanisms of disease Chemokines, chemotactic cytokines that mediate inflammation. N. Engl. J. Med. 338 436-445. 

Type II, III, and IV allergic reactions are variants of physiologic defense mechanisms only relevant in special situations, which follow a common pathologic pattern. In general, treatment of these forms require antiinflammatory ( inflammation) or immunosuppressive strategies ( immunosuppression). Therefore, only therapy of Type I reactions will be described here. 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Calpain inhibition may represent an important mechanism for future drug development. Control of calpain activity may limit the invasive properties of cells and thereby provides a possible mechanism to limit the invasiveness of tumors or inhibits the development of chronic inflammation. For the moment, pharmacological inhibitors of calpains are still not capable of differentiating among different calpain isoforms in cellular systems or in vivo. The importance of calpains in diseases will continue to stimulate the development of new and better inhibitors. 

Tuckermann JP, Kleiman A, McPherson KG et al (2005) Molecular- mechanisms of glucocorticoids in the control of inflammation and lymphocyte apoptosis. Crit Rev Clin Lab Sci 42 71-104... 

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