Cytokines inflammatory

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

Inflammation. Figure 1 Sequence of events in the recruitment of leukocytes in postcapillary venules adjacent to injured tissue. At the site of lesion, diverse reactive substances stimulate the endothelium to produce inflammatory cytokines, chemoattractants and other inflammatory mediators. The cytokine-activated endothelium expresses adhesion molecules that lead to the low affinity interactions between leukocytes and endothelium, which is mediated by selectins and described as rolling. Subsequently integrins mediate the firm adhesion of leukocytes, which allows emigration of the cells from venules into the interstitial compartment. Activated mast cells, PMNs and macrophages secrete cytokines (TNFa), lipid mediators (LTB4) and other inflammatory players (histamine, NO). 

Inflammatory caspases (caspase-1, -4, -5,-11 and -12) constitute a subgroup of the caspase family. Caspase-1 is the best characterized member and is responsible for the proteolytic maturation and release of the pro-inflammatory cytokines pro-interleukin (IL)-1 (3 and pro-IL-18. Caspase-1 gets activated in inflammasome complexes upon cellular stress, cellular damage and infection. 

IFN- 3 reduces the induction by inflammatory cytokines of adhesion molecules and of MHC class I and II complex on endothelial cells, a process preceding attachment and transendothelial migration of T-cells. These anti-inflammatory effects of IFN- 3 exemplify antagonistic actions of type I and type IIIFN. There is, indeed, much clinical evidence for the involvement of IFN-y in inflammatory processes - through activation of iNOS and subsequent secretion of NO - leading to the establishment of autoimmune diseases as for instance in rheumatoid arthritis. 

PAMPs and various tissue factors can prime DCs to produce T-cell-polarizing factors [21], IL-12 is a pro-inflammatory cytokine that induces IFN-y and promotes the development of Thl-cell differentiation [31], Other Thl-polarizing factors are IFN-a and IFN-(3 [32] and cell-surface expressed intracellular adhesion molecule (ICAM)-l [33]. On the other hand, it has been shown that NF-kB inducing kinase (NIK), which is known to regulate B-cell maturation and lymphoid organogenesis, is important for the induction of Thl7 cells [34],... 

Blum AS, Dal Pan GJ et al (1996) Low-dose zalcitabine-related toxic neuropathy frequency, natural history, and risk factors. Neurology 46(4) 999-1003 Bradley WG, Verma A (1996) Painful vascuhtic neuropathy in HlV-1 infection relief of pain with prednisone therapy. Neurology 47(6) 1446-1451 Breen EC (2002) Pro- and anti-inflammatory cytokines in human immunodeficiency virus infection and acquired immunodeficiency syndrome. Pharmacol Ther 95(3) 295-304 Bremer J (1990) The role of carnitine in intracellular metabolism. J Clin Chem Clin Biochem 28(5) 297-301... 

Evidence for a neuroimmunological involvement in Alzheimer s disease is accumulating. Activation of the complement cascade by beta amyloid (Rogers et al., 1992), the recruitment, proliferation and activation of microglia in intimate juxtaposition to the senile plaques (Davis et al., 1992), and the increased synthesis of microglia-derived pro-inflammatory cytokine interleukin-1 (Griffin et al., 1989) is indicative of a chronic inflam-... 

Pinnaa, G. F. Fiorucci, M. Reimund, J.-M. Taquet, N. Arondel, Y. Muller, C. D. Celastrol inhibits pro-inflammatory cytokine secretion in Crohn s disease biopsies. Biochem. Biophys. Res. Commun. 2004, 322, 778-786. 

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. 

In the late phase response, activated airway cells release inflammatory cytokines and chemokines, recruiting inflammatory cells into the lungs. The late phase response occurs 4 to 6 hours after the initial allergen challenge and results in a less intense bronchoconstriction as well as increased airway hyperresponsiveness and airway inflammation.6... 

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