Interleukin inflammation

A number of adipokines are linked to inflammation and immunity (Fig. 1). This includes both leptin and adiponectin, and also a number of other key inflammatory proteins, particularly cytokines and chemokines [1]. The cytokines and chemokines encompass interleukin-1(3 (EL-1 (3), IL-6, DL-10, TNFa, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF). Other major inflammation-related adipokines include nerve growth factor (NGF), and acute phase proteins such as serum amyloid A and haptoglobin. In addition, adipocytes secrete plasminogen activator inhibitor-1 (PAI-1), which is an important thrombotic factor as well as an acute phase protein. 

CD C14 C14.001 Caspase-1 Potential drug target for down-regulation of the inflammatory mediator, interleukin 1beta, which could ameliorate inflammation and endotoxic shock... 

Sergejeva S, Ivanov S, Lotvall J, Linden A Interleukin-17 as a recruitment and survival factor for airway macrophages in allergic airway inflammation. Am J Respir Cell Mol Biol 2005 33 248-253. 96 Bush KA, Farmer KM, Walker JS, Kirkham BW Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgGl Fc fusion protein. Arthritis Rheum 2002 46 802-805. 

These proteins are called acute phase proteins (or reactants) and include C-reactive protein (CRP, so-named because it reacts with the C polysaccharide of pneumococci), ai-antitrypsin, haptoglobin, aj-acid glycoprotein, and fibrinogen. The elevations of the levels of these proteins vary from as little as 50% to as much as 1000-fold in the case of CRP. Their levels are also usually elevated during chronic inflammatory states and in patients with cancer. These proteins are believed to play a role in the body s response to inflammation. For example, C-reactive protein can stimulate the classic complement pathway, and ai-antitrypsin can neutralize certain proteases released during the acute inflammatory state. CRP is used as a marker of tissue injury, infection, and inflammation, and there is considerable interest in its use as a predictor of certain types of cardiovascular conditions secondary to atherosclerosis. Interleukin-1 (IL-1), a polypeptide released from mononuclear phagocytic cells, is the principal—but not the sole—stimulator of the synthesis of the majority of acute phase reactants by hepatocytes. Additional molecules such as IL-6 are involved, and they as well as IL-1 appear to work at the level of gene transcription. 

J (2001) Green tea polyphenol extract attenuates inflammation in interleukin-2-deficient mice, a model of autoimmunity , J Nutr, 131 (7), 2034-9. 

Inflammatory cytokines have been implicated in the pathophysiology of HF.9 Several proinflammatory (e.g., tumor necrosis factor-a [TNF-a], interleukin-1, interleukin-6, and interferon-y) and anti-inflammatory cytokines (e.g., interleukin-10) are overexpressed in the failing heart. The most is known about TNF-a, a pleiotrophic cytokine that acts as a negative inotrope, stimulates cardiac cell apoptosis, uncouples 3-adrenergic receptors from adenylyl cyclase, and is related to cardiac cachexia. The exact role of cytokines and inflammation in HF pathophysiology continues to be studied. 

Eosinophils may be increased in some patients, particularly during exacerbations. Activated inflammatory cells release a variety of mediators, most notably leukotriene B4, interleukin-8, and tumor necrosis factor-a (TNF-a). Various proteinases, such as elastase, cathepsin G, and proteinase-3, are secreted by activated neutrophils. These mediators and proteinases are capable of sustaining inflammation and damaging lung structures. 

The inflammatory response in UC is propagated by atypical type 2 helper T cells that produce proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF).7 As discussed previously, a genetic predisposition to UC may partially explain the development of excessive colonic and rectal inflammation. The finding of positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) in association with the human leukocyte antigen (HLA)-DR2 allele in a large percentage of patients with UC supports this theory.4,12... 

Multiple factors play a role in the development of AOM. Viral infection of the nasopharynx impairs eustachian tube function and causes mucosal inflammation, impairing mucociliary clearance and promoting bacterial proliferation and infection. Children are predisposed to AOM because their eustachian tubes are shorter, more flaccid, and more horizontal than adults, which make them less functional for drainage and protection of the middle ear from bacterial entry. Clinical signs and symptoms of AOM are the result of host immune response and damage to cells caused by inflammatory mediators such as tumor necrosis factor and interleukins that are released from bacteria.4... 

Kraan MC, Patel DD, Haringman JJ, et al. The development of clinical signs of rheumatoid synovial inflammation is associated with increased synthesis of the chemokine CXCL8 (interleukin-8). Arthritis Res 2001 3(1) 65-71. 

Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999 103(6) 779-788. 

Steiner TS, Lima AAM, Nataro JP, Guerrant RL Enteroaggregative Escherichia coli produce intestinal inflammation and growth impairment and cause interleukin-8 release from intestinal epithelial cells. J Infect Dis 1998 177 88-96. 

An additional approach to IL-1 down-regulation could entail development of inhibitors of the proteolytic enzymes that release the active interleukin from its inactive precursor. Moreover, such inhibitors could probably be taken orally and, thus, would be suitable to treat chronic inflammation (the alternatives outlined above would be administered parenterally). 

Interleukins Various, mainly cells mediating immunity and inflammation... 

Local inflammatory changes occur in the joint capsule and synovium. The synovium becomes infiltrated with T cells, and immune complexes appear. Crystals or cartilage shards in synovial fluid may contribute to inflammation. There are also increased levels of interleukin-1, prostaglandin E2, tumor necrosis factor-a, and nitric oxide in synovial fluid. Inflammatory changes result in effusions and synovial thickening. 

Tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 are proinflamma-tory cytokines important in the initiation and continuance of inflammation. 

T-lymphocyte activation leads to release of cytokines from type 2 T-helper (TH2) cells that mediate allergic inflammation (interleukin [IL] -4, IL-5, and IL-13). Conversely, type 1 T-helper (THj) cells produce IL-2 and interferon-y that are essential for cellular defense mechanisms. Allergic asthmatic inflammation may result from an imbalance between THj and TH2 cells. 

In this new scenario much attention is being paid to the investigation of a series of markers of inflammation as reliable indicators of coronary risk. Their value is stressed by the observation that up to one third of events occurs in subjects without traditional risk factors. The C-reactive protein (CRP) seems to provide the strongest risk prediction for CHD in women (Albert 2000 Ridker 2001), although homocysteine, interleukin-6 (IL-6), and lipoprotein (a) [ Lp (a) ], among others, have each been independently associated with increased risk for CHD in women (for a review see Davison and Davis 2003 Rader 2000). 

Srivastava, K. D. et al. Crucial role of interleukin-1 beta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice. Am. J. Respir. Crit Care Med 165, 527, 2002. 

Holmin, S. and Mathiesen T. Intracerebral administration of interleukin-1 beta and induction of inflammation, apoptosis, and vasogenic edema. J. Neurosurg. 92, 108, 2000. 

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