The acute phase response refers to a coordinated series of reactions in response to a variety of stimuli and involves all major body systems. This generalized host response is characterized by fever, changes in local vascular permeability, modulation of hepatic protein synthesis and systemic metabolic changes. Regulation of the acute phase response is thought to be mediated primarily by cytokines. Furthermore, complex interactions exist between the activated cytokine network and neuroendocrine systems, providing additional regulatory pathways. The acute phase response may be transient and recover within a few days or, in case of persistence of the initiating stimulus, may be converted to a chronic phase of inflanunation (Fig. \\ ). Transition of the acute phase response to the chronic inflammatory state is frequently accompanied by the development of anaemia, defined as the anaemia of chronic disease [ACDj. ACD is associated with chronic infectious, inflammatory and neoplastic disorders and is a common cause of anaemia. The pathogenesis of ACD is complex and not entirely understood. Factors thought to be involved include inhibition of erythropoiesis, disturbance of iron metabolism and an impaired erythropoietin response to the anaemia. The induction of ACD is related to continuation of the inflammatory response, which might imply that ACD is an immunologically mediated phenomenon. Indeed, evidence has been obtained that proinflammatory cytokines are involved in the formerly mentioned pathophysiological mechanisms, although many of their postulated effects remain speculative. The purpose of the present thesis is to obtain more insight in the regulation of the acute phase response and the pathogenesis of ACD with respect to the role of cytokines, endocrine systems and iron metabolism. In tills perspective, the acute phase response and cytokine network are described in more detail in this chapter. Subsequently, current concepts of iron metabolism and the effects of inflammation are reviewed as well as pathogenetic, diagnostic and treatment aspects of ACD. Finally, the aims ofthe thesis wil be formulated.

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Erasmus University Rotterdam
H.G. van Eijk (Henk)
hdl.handle.net/1765/19751
Erasmus MC: University Medical Center Rotterdam

Feelders, R. (1999, March 24). Pathophysiological aspects of the acute phase response and the anaemia of chronic disease : with a focus on iron metabolism: With a focus on iron metabolism. Retrieved from http://hdl.handle.net/1765/19751