Inflammation Repair

Holgate S The inflammation-repair cycle in asthma The pivotal role of the airway epithelium. Clin Exp Allergy 1998 28(suppl 5) 97-103. 

Considering first the role of the material, if that material were totally inert chemically and unable to react at all with the tissues, and if the device were not able to irritate the tissues in any way, the perturbation to the inflammation/repair sequence is minimal, and the result will be the formation of a zone of fibrous tissue analogous to the scar, but oriented in such a way as to envelope the implant. The classical response to an implant is its encapsulation by soft fibrous tissue. On the other hand, if the material is able to react with the tissues, chemically, mechanically or any other way, it will act as a persistent stimulus to inflammation. While there is nothing inherently harmful about inflammation as a response to injury, persistent inflammation occurring as a response to a persistent injury is less acceptable. At the very least, this results in a continued stimulus to fibrosis such that the capsule is far more extensive and may intervene between the material and tissue it is meant to be in contact with (for example bone in the case of joint prostheses) but perhaps more importantly it can change the immediate tissue environment from one of quiescent fibrosis to that of active chronic inflammation. This is rarely the appropriate response and, as noted above, is likely to generate an even more aggressive environment. 

The bronchial epithelium is increasingly being shown to play a dynamic role in regulating the inflammation, repair, and remodeling process of asthma. It is well established as an important source of mediators including arachidonic acid products (15-HETE, PGE2), nitric oxide (NO) endothelins, cytokines (IL-ip, IL-5, IL-6, IL-11, GM-CSF, IL-16, IL-18) (93-98), chemokines (IL-8, Gro-a, MCP-1, MCP-3, RANTES, MIP-la, MIP-2, eotaxin, and eotaxin-2), and molecules involved in inflammation and repair. 

Histamine is a biogenic amine that is widely distributed in the body and functions as a major mediator of inflammation and allergic reactions, as a physiological regulator of gastric acid secretion in the stomach, as a neurotransmitter in the central nervous system (CNS) and may also have a role in tissue growth and repair. 

Inflammation occurs when a living tissue is injured or infected by microorganisms. It is a beneficial, self-limited response that requires phagocytic cells and elements of circulating plasma to enter the affected area. In principle it may achieve resolution and repair as the ideal outcome of inflammation. The persistent accumulation and activation of leukocytes is a hallmark of chronic inflammation. 

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. 

Lilly have recently introduced an anti-inflammatory drug opren (53) which may repair damage as well as reduce inflammation. Suggest a synthesis for (53). 

Fibrotic disease results from epithelial injury and abnormal wound repair in the absence of preceding inflammation. 

Mucins are also thought to act in cooperation with trefoil proteins in the protection and repair of the epithelium (Kindon et al., 1995). Trefoil factors are expressed along the GI tract and increased levels are noted near sites of inflammation and ulcerative lesions (Babyatsky et al., 1996). Furthermore, it has been demonstrated that mouse intestinal trefoil factor may play a role in the alteration of the physicochemical nature of GC mucins during N. brasiliensis infection (Tomita et al., 1995). Perhaps in GI nematode parasite infection mucins are not aiding in the host s protective expulsion of the parasite, but rather are functioning in the repair of the damaged intestinal epithelium. 

Holgate ST. Asthma a dynamic disease of inflammation and repair. Ciba Foundation Symposium 1997 206 5-28. 

Inflammation is the normal host response to infection or injury that mediates immune elimination of pathogens and tissue repair. Inflammatory processes include increased production of cytokines, chemokines, nitric oxide, and eicosanoids by the innate immune system in conjunction with altered leukocyte homing, all of which greatly impact acquired immunity. Aberrant inflammatory responses evoke both acute injury such... 

Thus, the role of cytokines in inflammation, immune-cell function and tissue repair is varied and complex. Later sections of this book explore the cytokines generated by neutrophils during inflammatory challenge ( 7.3.4), the regulation of neutrophil function by cytokines ( 7.2.1) and human diseases associated with neutrophil dysfunction in which cytokines may play important roles ( 8.2.5, 8.8). 

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