Interleukin anti-inflammatory action

Astragalus [Astragalus membranaceus) Uses Rx of resp infxns, enhancement of immune system, HF Action Root saponins T diuresis, BP anti-inflammatory action related to the stimulation of macrophages, T antibody formation T T-lymphocyte proliferation Available forms Caps/tabs 1-4 g ticl, PO Liq ext 4-8 mL/d (1 2 rado) dry ext 250 mg (1 8 ratio) dd, PO Notes/SE Immunosuppression w/ doses >28 g Interactions T Effect OF acyclovir, anticoagulants, antihypertensives, antithrombotics, antipits, interleukin 2, interferon i effect OF cyclophosphamide EMS T Risk of bleeding... 

During chronic inflammatory disease, inflammatory cells (neutrophils, mast cells, macrophages, and lymphocytes) become increasingly more damaging to tissues. Anti-inflammatory action of Bik reduces cell death mediated by immune cell. Proinflammatory cytokine tumor necrosis factor-a (TNF-q) and interleukin-1 (3 (IL-1) cause expression of multiple inflammatory and innate immunity genes for additional cytokines, chemokines, adhesion molecules, and enzymes. Aprotinin has been reported to cause a reduction in apoptosis in vivo by decreasing inflammatory cytokine expression (IL-1, IL-6, and TNF -a) thus preventing caspase-8 activation [81],... 

Takizawa, H., Desaki, M., Ohtoshi, T., Kawasaki, S., Kohyama, T., Sato, M., Tanaka, M., Kasama, T., Kobayashi, K., Nakajima, J., and Ito, K. (1995). Erythromycin suppresses interleukin 6 expression by human bronchial epithelial cells A potential mechanism of its anti-inflammatory action. Biochem. Biophys. Res. Commun. 210,781-786. 

Epinephrine and isoproterenol (via cAMP mechanisms) and theophylline (via cAMP or block of adenosine receptors) inhibit the release of mediators from mast cells and basophils and cause bronchodilation. Diphenhydramine competitively blocks histamine actions at H, receptors, actions that would otherwise cause bronchoconstriction and increased capillary permeability. Dexamethasone has multiple cellular effects, including inhibition of IgE-producing clone proliferation, block of T helper cell function, and anti-inflammatory actions. Most of the actions of glucocorticoids result from decreases in the synthesis of cytokines (eg, interleukins, platelet activating factor) or eicosanoids (leukotrienes, prostaglandins). 

The anti-inflammatory activity of the NSAIDs is mediated chiefly through inhibition of biosynthesis of prostaglandins (Figure 36-2). Various NSAIDs have additional possible mechanisms of action, including inhibition of chemotaxis, down-regulation of interleukin-1 production, decreased production of free radicals and superoxide, and interference with calcium-mediated intracellular events. Aspirin irreversibly acetylates and blocks platelet cyclooxygenase, while most non-COX-selective NSAIDs are reversible inhibitors. 

The principal mechanism of action is inhibition of dihydrofolate reductase, an enzyme important in the production of thymidine and purines. At the high doses used for chemotherapy, methotrexate inhibits cellular proliferation. However, at the low doses used in the treatment of inflammatory bowel disease (12-25 mg/wk), the antiproliferative effects may not be evident. Methotrexate may interfere with the inflammatory actions of interleukin-1. It may also stimulate increased release of adenosine, an endogenous anti-inflammatory autacoid. Methotrexate may also stimulate apoptosis and death of activated T lymphocytes. 

In addition to the inhibition of COX, lornoxicam shows weak inhibition of LPS-induced inducible nitric oxide synthase (iNOS IC50 65 pM) and LPS-induced interleukin-6 (IC50 54 pM), both of which could contribute to its potent anti-inflammatory and analgesic action (Berg et al., 1999). 

Molina-Holgado F, Pinteaux E, Moore JD, Molina-Holgado E, Guaza C, Gibson RM, RothweU NJ (2003) Endogenous interleukin-1 receptor antagonist mediates anti-inflammatory and neuroprotective actions of cannabinoids in neurons and glia. J Neurosci 23 6470-6474... 

The cytokines (peptide mediators of inflammation) are important intracellular messengers that play an important role in the inflammatory process. They have a short dnration of action and perform several diverse functions, such as growth regulation, cell division, inflammation, and immunity, by interacting with specific receptors present in different cells. " Cytokines can be of different classes and possess both pro- and anti-inflammatory properties. The interleukins (ILs) are cytokines prodnced by lenkocytes, which are important in the inflammatory process. The important proinflammatory cytokines include tumor uecrosis factor a (TNFa), interleukin-1 (IL-1), and interleukin-6 (IL-6). 

Figure 36-2. Sites of action of some anti-inflammatory drugs in a gouty joint. Synoviocytes damaged by uric acid crystals release prostaglandins (PGs), interleukins (ILs), and other mediators of inflammation Polymorphonuclear leukocytes (PMNs). macrophages, and other inflammatory cells enter the joint and also release inflammatory substances, including leukotrienes (eg, LTB ), that attract additional inflammatory cells. Colchicine acts on microtubules in the inflammatory cells. NSAIDs act on cyclooxygenase-2 in all of the cells of the joint.

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