Cytokines pro-inflammatory

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. 

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],... 

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. 

IL-1 7 T lymphocytes in synovium Synergistic effect with IL-1 andTNF leading to increased production of pro-inflammatory cytokines... 

RPE cells can express a number of anti-inflammatory and pro-inflammatory cytokines, and complement factors constitutively and/or upon stimulation (Chen et al., 2007 Crane et al., 2000a Ebihara et al., 2007 Holtkamp et al., 2001 Joffre et al., 2007). Therefore the effects of carotenoids on inflammatory responses are of great relevance to the retina. 

As already mentioned, van Kuijk and colleagues (Kalariya et al., 2008) tested the effects of oxidation products of [i-carotcnc, lutein, and zeaxanthin on the activation of redox-sensitive transcription factors, NF-kB, and AP-1 in cultured ARPE-19 cells. Degradation products of all three carotenoids induced activation of NF-kB and AP-1, and these effects were ameliorated by pretreatment of cells with 1 mM NAC. NF-kB is a major transcription factor that binds to promoter sites of many pro-inflammatory cytokines such as IL-1, IL-6, TNF-a, and iNOS. These results indicate that the degradation products of carotenoids can stimulate a pro-inflammatory pathway. 

Intratracheal instillation 14d Alveolar macrophages activation production pro-inflammatory cytokines Blood high-levels pro-inflammatory cytokines differentiation of CD4+ T cell to Thl and Th2 cells [108]... 

Upon activation, mast cells release numerous mediators, including vasoactive amines, proteases, pro-inflammatory cytokines (e.g. IL-ip, IL-6, IL-18 and TNF-a) and also regulatory Th2 cytokines (e.g. IL-4, IL-10 and IL-13) (Burd et al., 1989 Gordon and Galli, 1990 Marietta el al., 1996 Toru et al., 1998 Aoki et al., 1999 Lorentz et al, 2000). Therefore, the mastocytosis in the infected mucosa represents an immunopathological rather than a protective response. Indeed, our studies have shown that expulsion of T. spiralis from TNF-Rl / or iNOS / mice was achieved in the absence of a substantial mastocytosis and subsequent amelioration of enteropathy (Lawrence etal., 1998, 2000). 

The amount of released ET-1 peptide was different for the two cell types at basal conditions, and was not altered by the presence of pro-inflammatory cytokines. The presence of HU significantly decreased the ET-1 peptide release from these two cell types (52% and 64% reduction for TrHBMEC and EA-hy 926 cells, respectively) under basal culture conditions (Figure 11.2). The magnitude of reduction... 

Fig. 11.4 Dose-response effect of HU on ET-1 peptide release (a) from TrHBM EC cells incubated with various concentrations of HU during 48 h in the presence (A) and absence ( ) of cytokines (TNFaand IFNy at 100 U mL 1). Under the same conditions, quantitative mRNA analysis was also performed and the residual percentage of expression, in the presence (b) and absence (c) of pro-inflammatory cytokines is given.

Johnson R W (1997), Inhibition of growth by pro-inflammatory cytokines an integrated view , J Anirn Sci, 75, 1244-1255. 

A variety of medical conditions are now believed to be caused or exasperated by overproduction of certain cytokines in the body. A variety of pro-inflammatory cytokines, including IL-6, -8 and TNF,... 

It is a pro-inflammatory cytokine, promoting the synthesis of various substances such as eicosanoids, as well as proteases and other enzymes involved in generating inflammatory mediators. This appears to be its major biological function. 

Enbrel is a product now approved for medical use that is based upon this strategy. The product is an engineered hybrid protein consisting of the extracellular domain of the TNF p75 receptor fused directly to the Fc (constant) region of human IgG (see Box 13.2 for a discussion of antibody structure) The product is expressed in a CHO cell line from which it is excreted as a dimeric soluble protein of approximately 150 kDa. After purification and excipient addition (mannitol, sucrose and trometamol), the product is freeze-dried. It is indicated for the treatment of rheumatoid arthritis and is usually administered as a twice-weekly s.c. injection of 25 mg product reconstituted in WFI. Enbrel functions as a competitive inhibitor of TNF, a major pro-inflammatory cytokine. Binding of TNF to Enbrel prevents it from binding to its true cell surface receptors. The antibody Fc component of the hybrid protein confers an extended serum half-life on the product, increasing it by fivefold relative to the soluble TNF receptor portion alone. 

Several pro-inflammatory cytokines, such as TNFa, IL-1, IL-6, are important in the initiation and maintenance of various autoimmune diseases, such as RA, CD, and psoriasis. Thus, targeted therapies, which have been developed to inhibit their activity, have resulted in clinical improvement of these patients. Currently, there are three TNFa inhibitors (etanercept, infliximab, and adalimumab) and one IL-1 receptor antagonist (anakinra) that have been approved for the treatment of at least one of these diseases. In addition, a number of other anti-cytokine therapies are in clinical development. The TNFa antagonists will be reviewed here. 

CD8+CD69+ T cells was not observed in vivo. NK cells appeared to increase during the recovery period and an expansion of B cells was observed that persisted longer than that observed for T cells in individual animals. Transient, moderate elevations of serum IL-2, IL-5 (anti-inflammatory TH2-type cytokine), and IL-6 (inflammatory cytokine) was observed in individual animals at 2 or 24 hours following the initial dose but were not observed on Days 17 or 62 no changes in TNFa or IFNy (major pro-inflammatory cytokines) were observed. Thus, TGN1412 did not appear to be associated with a cytokine-release syndrome that has been observed in humans with upon administration of agonistic anti-CD3 antibodies.78... 

Early research showed that Pb exposure could increase sensitivity to bacterially-derived endotoxins [63] as well as increase production of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) by macrophages [64-67], Studies in several species indicate that Pb boosts production of TNF-a both immediately following adult exposure and in later life following gestational exposure. Flohe and coworkers [67] reported that Pb-induced elevation in TNF-a production is sensitive to both protein kinase C signaling as well as protein production. Not only can the production of TNF-a be elevated following exposure to Pb, but also the expression of the receptor for TNF-a (TNF-R) is elevated [68], Therefore, the combined effect of elevated cytokine production by macrophages as well as increased receptor expression would be expected to contribute to problematic inflammatory responses. 

Moos, A., Baecher-Steppan, L., and Kerkvliet, N., Acute inflammatory response to sheep red blood cells in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin The role of pro-inflammatory cytokines, IL-1 and TNF, Toxicol. Appl. Pharmacol., Ill, 331, 1994. 

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