Inflammatory events

Many low weight compounds produced by microor-ganism-like formylated peptides as well as endogenous mediators are chemotactic for leukocytes and promote the inflammatory process. The main endogenous compounds are listed in Table 1 and are derived from activated plasma protein cascades that function as amplification mechanisms, are performed and released from activated cells or are de novo synthesized on demand by cells participating in or being affected by inflammatory events. The major modulators of leukocyte adhesion to endothelial cells are listed in Table 2. 

Under normal physiological conditions, therefore, antioxidant defences in the skin are able to modulate free-radical production. The initiation of an inflammatory event has the potential for increasing ROS production to such an extent that defence systems are overwhelmed and tissue damage occurs. This event results in the production of even more toxic oxidants and the development of overt disease requiring treatment. Section 4 of this chapter will describe the role of ROS in skin inflammation. 

Several of the postulated roles for nematode-secreted AChEs assume that they gain access to the intestinal mucosa. Several possibilities exist for transport of parasite AChE across the epithelial cell barrier, such as (i) utilization of existing pathways for receptor-mediated transcytosis (ii) a paracellular route facilitated by parasite-secreted proteases as observed for a bacterial elastase (Azghani et al., 1993) and (iii) increased paracellular permeability resulting from inflammatory events in the mucosa. We consider the latter suggestion most likely, as this has been duplicated by ex vivo perfusion with rat mast cell protease II (Scudamore et al., 1995). Moreover, cholinergic stimulation attenuates epithelial barrier properties to macromolecules in rat ileal crypts (Phillips et al., 1987). 

By virtue of rendering iron catalytically inactive, dietary phytate may also suppress the incidence of colonic cancer (J2j>). Intestinal aerobic bacteria and/or minor inflammatory events generate substantial amounts of O27 leading to OH formation and lipid peroxidation. These two processes are thought to be important elements in tissue injury which occurs during inflammation. This argument is compatible with the observation that colonic cancer is frequently preceded, or accompanied, by pigmentation of the colonic epithelium lipofuscin, a byproduct of lipid... 

In hirman keratinocyte cultures, triethanolamine was categorized as a weak inducer of a delayed (> 4 h) stimulation of the release of key mediators (arachidonic acid, eicosanoids, interleukin-la) that are known to be indicative of hyperproliferative and inflammatory events in human skin (Miiller-Decker et al., 1994). In line with the in-vitro irritancy tests, triethanolamine was found to be a non-irritant in a clinical patch testing study of human skin in 20 male volunteers (Miiller-Decker et al., 1998). 

Mrsny, R.J., et al. 2004. Identification of hepoxilin A3 in inflammatory events A required role in neutrophil migration across intestinal epithelia. Proc Natl Acad Sci 101 7421. 

Tillie-Leblond I, Gosset P, Tbnnel AB. Inflammatory events in severe acute asthma. Allergy. 2005 60 23-29. 

In spite of the widespread occurrence of slgA, not only in cestode infections, but in all other helminth intestinal infections, the role played by IgA remains unknown (921). In relation to this, it has been speculated (53) that IgA antibody is relevant in the control of the uptake of parasite antigens, their clearance from the circulation and in the modulation of the activities of various cells in the inflammatory events associated with infections this may involve enhancement of cytotoxic functions or the minimization of potentially pathogenic reactions. ... 

Traumatic brain injury leads to inflammatory events that are believed to contribute to outcome through secondary injury mechanisms (67,68). 

Several cases have been reported in which herpes simplex virus keratitis developed after initiation of latanoprost therapy. Although these cases are anecdotal, it is known that prostaglandins may play a crucial role in mediating inflammatory events that could incite herpetic infection. 

Cyclosporine A (CsA, Restasis 0.05%) was approved in 2002 by the FDA as an ocular therapeutic for patients with keratoconjunctivitis sicca (dry eye). Until 2002 the therapy of choice for the treatment of dry eye was artificial tears and punctal plugs and the occasional use of pulse doses of topical steroids.Artificial tears and pimctal plugs brought some temporary relief to patients, but the underlying cause of dry eye, inflammation, was not affected. Steroids carried the threat of a multitude of side effects. With as many as 7.1 million people in the United States alone encountering dry eye symptoms, the development of a therapy that eliminates the inflammatory events associated with the disease has been a significant benefit. 

Inflammation of the ocular surfece is characterized by acute inflammatory events that occur within 24 hours of being exposed to an offending stimnlus and if not controlled can transform into a chronic inflammatory state. In an acnte response, in both the cornea and conjunctiva, physical injury to the eye can damage the epithelium, resulting in the release of proinflammatory cytokines from these cells (Fignres 12-8 and 12-9). Cytokines are proteins that serve as the main intermediaries of commnnication among cells of the immune... 

Redox status can be restored by the use of SH group donor, such as NAC, which is an antioxidant and SH group donor, and is also cell membrane permeable. It attenuates cytokine production in various experimental model systems both in vitro and in vivo [24, 49]. The search for molecules with good bioavailability and able to modulate redox status is very active with the target of therapies that not only protect against the injurious effects of oxidants, but also may fundamentally alter the inflammatory event. 

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