Inflammatory response, events

The objectives of the inflammatory response can be viewed as a hierarchical ordered panel of events. The most successful consequence of an inflammatory response is the complete restoration of function and structure of the affected tissue, also denoted as resolution. If this is not possible, inflammation aims for healing by repair and replacement of lost tissue by scar tissue. 

Chapman GA, Moores K, Harrison D, Campbell CA, Stewart BR, Strijbos PJ (2000) Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J Neurosci 20 RC87... 

The model concerning wound healing occurs in two phases (1) pro-inflammatory responses (Glaser and Kiecolt-Glaser 2005 Moore 1999 Tidball 2005 Whelan et al. 2005) which are needed to ensure adequate clearance of pathogen at the site of tissue injury, as well as, (2) re-epithelialization and neovascularization events (Frantz et al. 2005 Moore 1999 Naldini and Carraro 2005 Olah and Caldwell 2003 Whelan et al. 2005) to ensure proper wound closure. It is important to note that the resolution of pathogen clearance is essential in order for the wound closure processes to take place (Robson 1997). 

Chronic inflammation is a leading component and contributing event to the pathogenesis of fibrotic disease, where a normal inflammatory response to injury becomes a chronic, pathologic wound-healing response. 

Fig. 14.1. The Thl/Th2 balance is central to the regulation of normal wound repair. Tissue injury results in the initiation of an inflammatory response, mediated by a variety of cells and their by-products. Immune cells are recruited and cross-regulate the Thl/ Th2 balance that occurs in response to the cytokine environment. This balance is in turn cross-regulated by the chemokine/chemokine-receptor expression profile, which functions to amplify the inflammatory process. Cells residing in the injured tissue release profibrotic mediators, which promote fibroblast activation, proliferation, and differentiation to the myofibroblast phenotype. Myofibroblasts produce collagen to repair damaged tissue, which is an event that is favored by the inhibition of MMP activity. The Thl/Th2 balance is central to whether a normal or aberrant wound-repair process is established A Thl environment promotes normal tissue resolution (fibrinolysis), whereas a Th2 environment maintains the progression of fibrotic disease (excessive collagen deposition).

The regulation of mast-cell activity by biologically active peptides is an area of research, the rapid growth of which has been sparked in part by this intense interest in the interactions between neural, endocrine and immune systems [4, 26, 41] and in part by the recognition that activation of mast-cell secretion as a purely allergic IgE-dependent event is undoubtedly too restrictive. The involvement of the mast cell in the inflammatory response, for example, has for years been suspected to involve a number of non-immunologic, IgE-inde-pendent factors [24,42], Direct evidence for peptide involvement, however, has... 

Like nitric oxide, the discovery of the eicosanoid signalling molecules was a significant event in twentieth century physiology, due largely to research led by Sir John Vane (Nobel Prize 1982). The diverse actions of the eicosanoids include roles in muscle contraction, blood coagulation, salt and fluid homeostasis, inflammatory responses and pain sensitivity. 

Inflammation is characterized by the orderly occurrence of several processes initiation of the event by a foreign substance or physical injury, recruitment and chemoattraction of inflammatory cells, and activation of these cells to release inflammatory mediators capable of damaging or killing an invading microbe or tumor. In some instances, the inflammatory response is initiated by an otherwise harmless foreign material (e.g., pollen). Inflammation can also result from an autoimmune response to the host s own tissue, as occurs in rheumatoid arthritis. 

Serious adverse events occur in up to 6% of patients with anti-TNF therapy. The most important adverse effect of these drugs is infection due to suppression of the ThI inflammatory response. This may lead to serious infections such as bacterial sepsis, tuberculosis, invasive fungal organisms, reactivation of hepatitis B, listeriosis, and other opportunistic infections. Reactivation of latent tuberculosis, with dissemination, has occurred. Before administering anti-TNF therapy, all patients must undergo purified protein derivative (PPD) testing prophylactic therapy for tuberculosis is warranted for patients with positive test results. More common but usually less serious infections include upper respiratory infections (sinusitis, bronchitis, and pneumonia) and cellulitis. The risk of serious infections is increased markedly in patients taking concomitant corticosteroids. 

Weigel, P.H., Fuller, G.M., and LeBoeuf, R.D., A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing. J. Theor. Biol., 119, 219, 1986. 

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