Proinflammatory mediators

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

We have identified mast cells around blood vessels and between myocardial fibers in all sections of human hearts [16,17]. These cells are also seen in normal and atherosclerotic human arterial intima [ 18-21 ]. In situ electron microscopy of cardiac mast cells revealed a small percentage (about 5%) of activated, i.e. partially degranulated mast cells [16,22]. This is clinically relevant because it implies that immunologic and non-immunologic stimuli can activate HHMC to release vasoactive and proinflammatory mediators [23]. 

Whey proteins are known to increase immune response and maintain muscle mass (Phillips et ah, 2009). In one instance, when an immunosti-mulatory vitamin and mineral mixture developed at Tufts University Human Nutrition Research Center on Aging was blended with texturized WPI (TWPI) in an extruded snack bar, immunostimulatory effects were enhanced in young (< 5 months) and old (> 22 months) mice fed ad libitum for 5 weeks. The mineral mixture and TWPI improved T cell proliferation and reduced upregulated production of proinflammatory mediators in... 

Th2 lymphocytes are one of the primary factors initiating and perpetuating the inflammatory response.7 In addition, proinflammatory mediators such as the leukotrienes generated during mast cell degranulation can increase vascular permeability, leading to airway edema and increased mucus production.8 Eosinophilic infiltration of the airways is a hallmark of asthma, and activated eosinophils can cause bronchoconstriction and AHR.9... 

Chemokines are a superfamily of low-molecular-weight chemotactic cytokines that exert their effects through seven transmembrane domain G protein-coupled receptors. Although some chemokines are constitutively expressed in certain settings, most are induced by proinflammatory mediators, such as IFN-y and TNF-a. Upon binding to the appropriate receptor, chemokines initiate a... 

Triethanolamine has been clinically tested with other model irritant compoimds for potency to stimulate signal release of proinflammatory mediators in hrnnan skin in order to find biomarkers of irritancy. Neat or aqueous triethanolamine was applied to the lower arm of 12 male volimteers after 24 h, suction blister fluid specimens were taken from the site of treated skin. Triethanolamine caused no significant increase in arachidonic acid and prostaglandin concentrations in suction blister fluid samples, in... 

It has been shown that fish oil can not only suppress proinflammatory mediators but also can increase the anti-inflammatory ones such as adiponectin (Duda et al., 2009 Kalupahana et al., 2010b). Increased adipo-nectin levels can reduce inflammation and beneficially improve the metabolism. Specifically, the increased levels of adiponectin can significantly reduce the insulin resistance. Oster et al. (2010) showed that DHA increases cellular adiponectin mRNA and secreted adiponectin protein in 3T3-L1 adipocytes, possibly by a mechanism involving PPARy. A recent dietary intervention study conducted on healthy Japanese female subjects by Kondo et al. (2010) showed that a fish-based diet intervention increased the serum adiponectin concentration in young, nonobese, healthy Japanese female subjects. Also, the same study indicated that the increment in serum -3 PUFA may regulate the serum adiponectin concentration (Kondo et al., 2010). 

From clinical observations and from experimental data we know that the primary situation after eye bums results in severe release of proinflammatory mediators. These mediators start the disastrous disease that leads to loss of sight by chronic inflammation. This can be measured in vivo and ex vivo on Prostaglandins as showed in an eye bum model on rabbits in Fig. 5.16. 

There is some evidence that adenosine also participates in modulating peripheral somatosensory function through A3 receptors on immune cells. A predominant response to the activation of A3 receptors is degranulation of mast cells causing the release of multiple proinflammatory mediators (IL-6/IL-10/IL-12). Further involvement of A3 receptors in pain and inflammation may be a result of adenosine-mediated inhibition of the release of tumor necrosis factor a (TNF-a), a proinflammatory cytokine produced by monocytes and macrophages. 

In humans, chronic inflammation of the liver is associated with hepatitis B virus (HBV) infections, and this inflammation is considered an important contributing event in HBV-induced liver cancer. In animal models, there is evidence that inflammation contributes to tumor promotion. Treatment of mouse skin with TPA produces an inflammatory response and increases the expression of proinflammatory mediators such as TNF-a, IL-la GM-CSF, and cyclooxygenase-2 (COX-2). Genetically modified mice deficient in TNFa or COX-2 are resistant to TPA-induced tumor promotion. These results indicate that the inflammatory effects of TPA are important in tumor promotion. 

Buxton, K.L., Babin, M.C., Ricketts, K.M., Gazaway, M.Y., Blank, J.A., Danne, M.M. (2000). Characterization of sulfur mustard-induced proinflammatory mediator response in mouse ears. Toxicologist 54 213. 

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