The acute inflammatory response

The migration of phagocytic cells to the site of damage is one of the most fundamental components of the acute inflammatory response, and the key players in this process will be presented next. 

In the very early phases of the acute inflammatory response most of the cells invading the damaged area are polymorphonuclear neutrophils, also denoted as PMNs, which serve as initial line of defense and source of proinflammatory cytokines. These cells, which usually live for 4-5 days, circulate in the blood until they are attracted by chemokines into injured tissues. Whereas physical injury does not recruit many neutrophils, infections with bacteria or fungi elicit a striking neutrophil response. The characteristic pus of a bacterial abscess is composed mainly of apoptotic (apoptosis) and necrotic PMNs. Emigration of neutrophils from the blood starts with a process denoted as margination where neutrophils come to lie at the periphery of flowing blood cells and adhere to endothelial cells (Fig. 1). L-Selectin is expressed... 

After 7 days, the acute inflammatory response at the implantation site was evaluated. Bisphenol A resulted in a moderate level of irritation at the implantation site and was clearly the least biocompatible test substance. Tyrosine derivatives containing the benzyloxycar-bonyl group caused a slight inflammatory response, while all other tyrosine derivatives produced no abnormal tissue response at all. These observations indicate that tyrosine dipeptide derivatives, even if fully protected, are more biocompatible than BPA, a synthetic diphenol. ... 

In addition to minimizing the acute inflammatory response, rest prevents additional injury to the affected area.13 The properties of the muscle-tendon unit are altered during the acute injury, with limitations on the ability of the muscles and tendons to stretch. Early activity predisposes a patient to further injury, but prolonged inactivity can lengthen recovery times. 

Peritonitis is defined as the acute inflammatory response of the peritoneal lining to microorganisms, chemicals, irradiation, or foreign-body injury. This chapter deals only with peritonitis of infectious origin. 

Dietary copper deficiency increases the acute inflammatory response in rats and other small laboratory animals (Schuschke et al. 1994). The release of inflammatory mediators, such as histamine and serotonin, from mast cells increases the vascular permeability of postcapillary venules and results in edema. In copper-deficient rats, release of histamine from mast cells correlates positively with frequency of the acute inflammatory response. Copper-deficient rats (0.6 mg Cu/kg DW ration for 4 weeks) have more mast cells in muscle than copper-adequate controls given diets containing 6.3 mg Cu/kg DW ration however, histamine content of mast cells is not affected (Schuschke et al. 1994). An early clinical sign of copper deficiency is a reduction in the number of circulating neutrophils the mechanism for copper-deficient neutropenia (leukopenia in which... 

Figure 1.8 Tissue section at implant site showing the effect of NO evolution on the acute inflammatory response, (a) Sensor with no NO evolution (control) (b) no evolution for about 18h. Reprinted with permission from Ref. 65. Copyright 2005 John Wiley Sons. (See the color version of this figure in Color Plates section.)...

D. Hohr, Y. Steinfartz, R. P. F. Schins, A. M. Knaapen, G. Martra, B. Fubini, and P. J. A. Borm, The surface area rather than the surface coating determines the acute inflammatory response after instillation of fine and ultrafine TftlE in the rat, Int. J. Hyg. Environ. Health 205, 239-244 (2002). 

The acute inflammatory response (see Table 14.1) leads to inflammation, redness, swelling, heat and pain, due to extravasation (leakage) of plasma and infiltration of leukocytes into the site of inflammation. Mechanisms that allow cells and proteins to gain access to damaged or infected extravascular sites include ... 

The acute inflammatory response requires constant stimulation if it is to be sustained. Inflammatory mediators have short half-lives and are quickly degraded in the tissue. Hence, inflammation ceases once the stimulus has been removed. 

Peritonitis is defined as the acute, inflammatory response of peritoneal lining to microorganisms, chemicals, irradiation, or foreign body injury. Peritonitis may be classified as either primary or secondary. With primary peritonitis, an intraabdominal focus of disease may not be evident. In secondary peritonitis, a focal disease process is evident within the abdomen. An abscess is a purulent collection of fluid separated from surrounding tissue by a wall consisting of inflammatory cells and adjacent organs. It usually contains necrotic debris, bacteria, and inflammatory cells. 

NSAIDs can mask signs of infection, such as fever and pain, which can delay appropriate treatment. Furthermore they can impair the host defence mechanism against infection and can modulate the acute inflammatory response in such a way as to alter the course of infection, predisposing the patient to bacteremia, shock, and multiorgan failure (212,213). Until appropriate studies have defined the relation between NSAIDs and severe soft tissue infections, it is better to avoid using them, if possible, until the cause of the fever is known. 

However, the central paradox in our consideration of inflammatory disease is that the inflammatory response evolved as a highly effective component of the innate immune response of the body to infection or injury. Indeed, until the last two or three decades, inflammation was perceived as an entirely beneficial host response to injury or infection. Elias Metchnikoff, the fether of modern inflammatory cell biology, emphasized this concept in his work. Neutrophil and eosinophil granulocytes play key defensive roles in infections such as lobar streptococcal pneumonia and in parasitic infestations such as schistosomiasis. The acute inflammatory response in... 

Andersson, P. B., Perry, V. H., and Gordon, S., The acute inflammatory response to lipopolysaccharide in CNS parenchyma differs from that in other body tissues, Neuroscience, 48, 169, 1992. 

Stimulation of cultured endothelial cells with thrombin, histamine, or H202 results in a rapid (within minutes) translocation of P-selectin (CD62P) to the cell surface from secretory granules known as Weibel-Palade bodies. In contrast, induction of endothelial E-selectin (CD62E) expression is dependent upon de novo synthesis following stimulation with cytokines such as IL-1 a and TNF-a.57 58 P- and E-selectin are only transiently expressed on the cell surface, during which time they bind to the sialylated Lewis X antigens of neutrophils and monocytes.59-61 Both selectins are implicated in leucocyte extravasation associated with the acute inflammatory response.62-63... 

MCWILLIAM, A.S., NELSON, D THOMAS, J.A. HOLT, P.G. (1994) Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. Journal of Experimental Medicine, 179, 1331-1336. 

Cover C, Liu J, Farhood A, Malle E, Waalkes MP, Bajt ML, Jaeschke H (2006) Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 216 98-107... 

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