Interleukin-lp

It was found that the HIV envelope glycoprotein in vitro increases the production of NO by human monocyte-derived macrophages [114]. NO production is increased in patients who have AIDS [115], and the increased concentrations of nitrite in AIDS patients with opportunistic infections is caused by T gondii, Pneumocystis carinii, Mycobacterium tuberculosis, and Mycobacterium avium, whereas nitrite concentrations are normal in symptom-free patients. It was also confirmed that there was increased production of NO in the sera of children with HIV-1 infection, and of circulating cytokines, such as interleukin lp, tumor necrosis factor a, and interferon y. It is postulated that rises in the concentrations of these cytokines may represent a substantial stimulation of NO production [116]. In contrast, it has been shown that there was no altered endogenous nitrate formation in eight patients with AIDS, most of whom had opportunistic infections [117]. It has also been noted that there were high... 

Interleukin-lp converting enzyme (ICE, which converts the M, 33,000 protease form of interleukin-ip to the active M, 17,500 form by cleaving after Asp residues) and other members of the ICE-like family of proteases appear to play a significant role in A. For example, expresrion of CrmA protein (a protease inhibitor that inhibits ICE) potently blocks the A. induced by stimulation of Fas or TNF-1, implying that ICE-type proteases are involved in these suicide pathways. Proteins identified as early targets or death substrates associated with the onset of A. are poly(ADP-ribose) polymerase, lamin Bl, a-fodrin, topoisomerase I, p-actin, and the Af, 70,000 compo nent of the U1 small ribonucleoprotein (Ul-70kD). 

Ohshima Y, Yang LP, Uchiyama T, Tanaka Y, Baum P, Sergerie M, Hermann P, Delespesse G 0X40 costimulation enhances interleukin-4 (IL-4) expression at priming and promotes the differentiation of naive human CD4i- T cells into high IL-4-producing effectors. Blood 1998 92 3338-3345. 

Interleukin-6 (IL-6) is a small polypeptide with a molecular mass of 26 kDa (see Table 2). IL-6 can be induced in various cell types, including fibroblasts, macrophages/monocytes, epithelial cells, T cells, B cells, and diverse tumor cells (L4). TNF, IL-1, and LPS can stimulate IL-6 gene expression in macrophages/monocytes and fibroblasts. In vivo studies showed that systemic administration of TNF, LPS, and IL-1 was followed by a rapid induction of circulating IL-6 (B49, J2). Also, endothelin (ET) at concentrations observed pathophysiolog-ically may trigger production of IL-6 (Ml7). 

Interleukin-10 (IL-10) affects antigen presentation capacity but also interferes with many other functions of monocytes and macrophages (Table 2) (F8). In vitro, IL-10 is a potent inhibitor of cytokine production, including production of TNF, IL-1, IL-6, and IL-8 by LPS-activated monocytes/macrophages (F8). It also inhibits tissue factor-dependent procoagulant activity induced by LPS in human... 

Reported applications of SASD involve modification of lipopolysaccharide (LPS) molecules and studying their interaction with albumin and an antibody directed against LPS (Wollenweber and Morrison, 1985), identification of the murine interleukin-3 receptor and an N-formyl peptide receptor (Sorenson et al., 1986), crosslinking of factor V and Va to iodinated peptides... 

IL-la and -ip are expressed as large (30 kDa) precursor molecules from which the mature polypeptide is released by proteolytic cleavage. Neither IL-la and -lp possess any known secretory signal peptide, and the molecular mechanism by which they exit the cell remains to be characterized. Neither interleukin appears to be glycosylated. 

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). 

Stimulation for 24 hours with LPS leads to the release of interleukin-1 [3, IL-6, IL-8, TNF-a and by prolonging the incubation period from 48 to 72 hours, the whole blood model can detect the release of other lymphokines [45], including IL-2, IL-4, IL-13 and IFN-y. Skewing of the T-helper cell response to antigens can likewise be detected by evaluating the pattern of cytokine release, corresponding to a predominance of Th 1 or Th2 cytokine production. The predictive value of these approaches is currently under investigation. 

Horai, R. et al., Production of mice deficient in genes for interleukin (IL)-la, IL-ip, and IL-1 receptor antagonist shows that IL-lp is crucial in turpentine-induced fever development and glucocorticoid secretion, J. Exp. Med., 187, 1463, 1998. 

In addition to directly eliciting cell chemotaxis and free-radical production, PAF can also induce the release of various inflammatory cytokines, amongst which tumour necrosis factor (TNF) is of particular importance [ 312 ]. We have recently shown that PAF stimulates TNF production from peripheral blood derived monocytes and at picomolar concentrations amplifies lipopoly-saccharide (LPS)-induced TNF production, effects inhibited by various PAF antagonists [313]. PAF also acts synergistically with interferon-y (IFN-y) to increase the monocyte cytotoxicity. Furthermore, PAF can modulate the production of both interleukin 1 and interleukin 2 (IL-1, IL-2) from rat monocytes and lymphocytes, respectively [222, 223], cytokines which in turn elicit the release of other mediators and growth factors. 

Andersen LP, Hoick S, Janulaityte-Gunther D et al (2005) Gastric inflammatory markers and interleukins in patients with functional dyspepsia, with and without Helicobacter pylori infection. FEMS Immunol Med Microbiol 44(2) 233-238... 

Endotoxicity results from the interaction of a bacterial cell envelope component (e.g., LPS or PG with a cell surface receptor constituting part of the nonspecific immune system, (i.e., a toll-like receptor on white blood cells). This results in the production of cytokines [e.g., interleukin 1 (IL-1) or tumor necrosis factor (TNF)] as part of an intracellular enzyme cascade which can cause severe tissue injury. Bioassays or immunoassays can be used to detect such reactions respectively. As noted above the most widely used bioassay is the LAL assay. A lysate of amoebo-cytes of the horseshoe crab (Limulus) contains an enzymatic clotting cascade which is activated by extremely low levels of LPS (nanogram levels or lower). There are variants of this assay that can detect PG, but they are not as widely used. As noted above, other bioassays employ cultured cell lines that respond to LPS or PG, respectively. Unfortunately bioassays are highly amenable to false positives (from the presence of cross-reactive substances) or false negatives from inhibition (by contaminants present in the sample) [10]. A detailed discussion of these assays is beyond the scope of this chapter and has been reviewed elsewhere [1]. 

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). 

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