Cytokine activity

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). 

Baiillari G, Gendelman R, Gallo RC, Ensoli B (1993) The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the ROD amino acid sequence. Proc Natl Acad Sci USA 90(17) 7941-7945... 

Activated T cells begin releasing cytokines including interleukin-2 (IL-2), interferon-y, (IFN-y), tumor necrosis factor (TNF-a), and others.4,13 Cytokine activity leads to a rapid proliferation and turnover of skin cells, triggering the inflammatory process and the development of psoriatic skin lesions.4,13,14 TNF-a may have a role in disease severity it upregulates endothelial and keratinocyte expression of ICAM-1,... 

Many of the manifestations of intraabdominal infections, particularly peritonitis, result from cytokine activity. Inflammatory cytokines are produced by macrophages and neutrophils in... 

Yamashiro S, Wang J-M, Gong W-H, Yan D, Kamohara H, Yoshimura T. Expression of CCR6 and CD83 by cytokine-activated human neutrophils. Blood 2000 96 3958-3963. 

Rollins BJ, Yoshimura T, Leonard EJ, Pober JS. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-l/JE. Am J Pathol 1990 136(6) 1229-1233. 

Wang JM, Sica A, Peri G, et al. Expression of monocyte chemotactic protein and interleukin-8 by cytokine-activated human vascular smooth muscle cells. Arterioscler Thromb 1991 11(5) 1166—1174. 

C8. Carlos, T Swartz, R Kovach, N. L., Yee, E., Rosso, M., Osbom, L. C Rosso, G., Newman, B Lobb, R., and Harlan, J., Vascular cell adhesion molecule-1 (VCAM-1) mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood 76, 965-970 (1990). 

Recently, it has been shown that inhalation of MWNTs caused suppression of the systemic immunity without resulting in significant lung inflammation or tissue damage [82,83]. Inhaled MWNTs in fact modified the functionality of spleen cells in exposed mice [82]. Notably, the activity of cyclooxygenase (COX) enzymes in spleen was affected as a response to a cytokine (TGF(5) released from the lungs. This cytokine activated the COX pathway in the spleen, triggering T-cell dysfunction and systemic immunosuppression [83]. 

Inhibition of cytokine activity in vivo by administration of monoclonal antibodies (and, more recently, by gene knockout studies) continues to elucidate the physiological and pathophysiological effect of various cytokines. 

Thl Soluble Antigen presented by MHC II Clonal expansion CD4Thl Thl cells activated, release cytokines, activate macrophages, inflammation Tuberculin Rx, contact dermatitis, berylliosis... 

The activity of p38/SAPK is central to the genetic changes that occur in response to cytokine activated pro-inflammatory signaling in astrocytes and microglia. p38/SAPK... 

Other protein kinases may indirectly influence the activation of NF-kappap. For example, in contrast to the pro-inflammatory effects typically observed with activation of kinases, the elevation ofcAMP activates PKA and blocks transcription of iNOS mRNA [51,178, 229, 230]. Astrocytes contain a variety of NT receptors that are coupled to Gs-adenylate cyclase [231] and, either activation of P-adrenergic/dopamine receptors or employing agents that increase cAMP, such as forskolin (adenylate cyclase activator), PDE inhibitors [i.e. pentoxifylline], dibutyrl cAMP, or 8-bromo cAMP can attenuate lipopolysaccharide (LPS)/cytokine activated iNOS mRNA in microglia, astrocytes and a number of other cell types [51,176,177,178, 232-237]. In contrast, agents that suppress the intracellular concentration of cAM P such as H-89 and Rp-cAM P are pro-... 

After damage or infection, monocytes and KCs in the area detect the damaged cells or infectious agent and respond with release of primary mediators such as TNFa, IL-1 and some IL-6. These cytokines activate the surrounding cells, that respond with a secondary, amplified release of cytokines. This second wave includes large amounts of IL-6, which induce the synthesis of acute phase proteins in hepatocytes and chemoattractants such as IL-8 and MCP-1. These events will then lead to the typical inflammatory reactions. Both IL-1 and TNFa activate the central regulatory protein of many reactions involved in immunity and inflammation, nuclear factor kappa B (NFkB). These cytokines cause dissociation of NFkB from its inhibitor IkB, which makes translocation of NFkB to the nucleus possible. In the nucleus active NFkB induces the transcription of the second wave cytokines (see also Chapter 7 for the molecular mechanisms of cytokine-mediated cell activation). 

Inflammatory cytokine activity — the lL-1 receptor and TNF receptor up-regulated. 

Table 5.7. Cytokines for which soluble receptors have been detected in biological fluids. The exact functional role played by these binding proteins, in modulating cytokine activity, remains to be elucidated in most cases...

Interferon IFN Type of cytokine, activates many types of immune cells... 

The effect of echinacea on the immune system is controversial. In vivo human studies using commercially marketed formulations of E purpurea have shown increased phagocytosis, total circulating white blood cells, monocytes, neutrophils, and natural killer cells but not immunostimulation. In vitro, Epurpurea juice increased production of interleukins-1, -6, and -10, and tumor necrosis factor- by human macrophages. Enhanced natural killer cell activity and antibody-dependent cellular toxicity was also observed with E purpurea extract in cell lines from both healthy and immunocompromised patients. Studies using the isolated purified polysaccharides from Epurpurea have also shown cytokine activation. Polysaccharides by themselves, however, are unlikely to accurately reproduce the activity of the entire extract. 

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