The Inflammatory process involves a series of events that can be elicited by numerous stimulate (e.g., infectious agents, ischemia, antigen- antibody interactions, and thermal or other physical injury). Each type of stimulus provokes a characteristic pattern of response that represents a relatively minor variation on a theme. At a macroscopic level, the response usually is accompanied by the familiar clinical signs of erythema, edema, tenderness (hyperalgesia), and pain. (Gallin et al., 1992)
Inflammatory responses occur in three distinct phases, each apparently mediated by different mechanisms: i-an acute transient phase, characterized by local vasodilatation and increased capillary permeability. ii- a delayed, sub acute phase, most prominently characterized by infiltration of leukocytes and phagocytic cells; and iii- a chronic proliferative phase, in which tissue degeneration and fibrosis occur. l many different mechanisms are involved in the inflammatory process. The ability to mount an inflammatory responses is essential for survival in the face of environmental pathogens and injury. Although in some situation and diseases the inflammatory response may be exaggerated and sustained for no apparent beneficial reason. (Kelly et al., 1993)
Histamine was one of the earliest mediators of the inflammatory process identified. Although several H, histamine receptor antagonists are available, they are useful only for the treatment of vascular events in the early transient phase of inflammation). Bradykinin and 5-hydroxytryptamine (serotonin, 5-HT) also may play a role in mediating inflammation, but their antagonists ameliorate only certain types of inflammatory responses. Specific inhibitors of leukotriene synthesis, (zileution, A 5-lipoxygenase inhibitor) and cysteinyl leukotriene-receptor antagonists (montelukast and zafirlukast) exert anti-inflammatory actions and have been approved for the treatment of asthma. Another lipid autacoids, platelet-activating factor (PAF), has been implicated as an important mediator of inflammation, and inhibitors of its synthesis and action are under study.(Metcalf et al., 1991)
The effects produced by intradermal, intravenous, or intraarterial injections of small amounts of prostaglandins are strongly reminiscent of inflammation. Prostaglandin E2 (PGE2) and prostacyclin (PGI2) cause erythema and an increase in local blood flow. With PGE2, such effect may persist for up to 10 hours, and they include the capacity to counteract the vasoconstrictor effects of substance such as nor epinephrine and angiotensin. These properties are not generally shared by other inflammatory mediators. In contrast to their long-lasing effects on cutaneous vessels and superficial veins. Prostaglandin-induced vasodilatation in other vascular beds vanishes within a few minutes.(Dinarello et al., 1992)
Although PGE1 and PGE2 cause edema when injected into the hind paw of rats, it is not clear if they can increase vascular permeability (leakage) in the post capillary and collecting venules without the participation of other inflammatory mediators (e.g bradykinin, histamine, leukotriene C4. furthermore, PGE1 is not produced in significant quantities in human beings in vivo, except under rare circumstance, such as essential tatty acid deficiency. Prostaglandins are unlikely to be directly involved in chemo tactic responses, even though they may promote the migration of leukocytes into an inflamed area by increasing blood flow. One potent chemo tactic substance, leukotriene B4, is a product of the 5-lipoxygenase pathway of arachidonate metabolism. Although high concentrations of NSAIDs can inhibit cell migration, this is not due to an ability of these drugs to inhibit 5-lipoxygenase and thus leukotriene B4 formation.( Mc Adam et al., 1999)
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