Physical exercise, inflammatory process and adaptive condition: an overview <s> ACUTe PhAse ResPONse (APR) <s> The acute phase response is an orchestrated response to tissue injury, infection or inflammation. A prominent feature of this response is the induction of acute phase proteins, which are involved in the restoration of homeostasis. Cytokines are important mediators of the acute phase response. Uncontrolled and prolonged action of cytokines is potentially harmful, therefore mechanisms exist which limit the activity of cytokines; these include soluble cytokine receptors and receptor antagonists. The cytokine signal is transmitted into the cell via membrane-bound receptors. Different intracellular signalling pathways are activated by different cytokine-receptor interactions. Eventually, cytokine-inducible transcription factors interact with their response elements in the promotor region of acute phase genes and transcription is induced. Systemic inflammation results in a systemic acute phase response. However, local inflammatory or injurious processes in the liver may also induce an acute phase response, for example after partial hepatectomy and during hepatic fibrosis. The acute phase proteins induced in these conditions probably act to limit proteolytic and/or fibrogenic activity and tissue damage. The possible function of the acute phase protein alpha 2-macroglobulin in hepatic fibrosis is discussed in some detail. <s> BIB001 </s> Physical exercise, inflammatory process and adaptive condition: an overview <s> ACUTe PhAse ResPONse (APR) <s> A decrease in serum albumin concentrations is an almost inevitable finding in disease states, and is primarily mediated in the acute phase by alterations in vascular permeability and redistribution. This change is not disease specific but marked changes that persist are generally associated with a poorer prognosis. Critical appraisal of long-standing practices and the availability of alternative colloid solutions have led to a reduction in albumin replacement therapy, and a widespread tolerance of lower albumin concentrations in patients. The factors determining serum albumin concentrations, their measurement and the implications of hypoalbuminaemia are reviewed. The clinical value of serum albumin measurement is discussed. <s> BIB002 </s> Physical exercise, inflammatory process and adaptive condition: an overview <s> ACUTe PhAse ResPONse (APR) <s> AbstractCytokines are soluble glycoproteins that are produced by and mediate communication between and within immune and nonimmune cells, organs and organ systems throughout the body. Pro- and anti-inflammatory mediators constitute the inflammatory cytokines, which are modulated by various stimuli, including physical activity, trauma and infection. Physical activity affects local and systemic cytokine production at different levels, often exhibiting striking similarity to the cytokine response to trauma and infection.The present review examines the cytokine response to short term exercise stress, with an emphasis on the balance between pro- and anti-inflammatory mechanisms and modulation of both innate and specific immune parameters through cytokine regulation. The effects of long term exercise on cytokine responses and the possible impact on various facets of the immune system are also discussed, with reference to both cross-sectional and longitudinal studies of exercise training. Finally, the validity of using exercise as a model for trauma and sepsis is scrutinised in the light of physiological changes, symptomatology and outcome, and limitations of the model are addressed.Further studies, examining the effect of exercise, trauma and infection on novel cytokines and cytokine systems are needed to elucidate the significance of cytokine regulation by physical activity and, more importantly, to clarify the health implications of short and long term physical activity with respect to overall immune function and resistance to infection. <s> BIB003 </s> Physical exercise, inflammatory process and adaptive condition: an overview <s> ACUTe PhAse ResPONse (APR) <s> The acute-phase response consists in a large number of behavioural, physiologic, biochemical, and nutritional changes involving many organ systems distant from the site, or sites, of inflammation. One of the most investigated, but still not well understood, characteristic of the acute phase is the up-regulation, or down- regulation, of many plasma proteins, known as the acute-phase proteins. The changes in the concentrations of these positive acute-phase proteins and negative acute-phase proteins are due to changes in their liver production. Their increase may vary from 25 percent to 1000 fold, as in the case of C-reactive protein and serum amyloid A. This review summarises the recent advances that have been acquired on the acute-phase proteins, in particular their function in pathologies such as infections or inflammatory lesions. <s> BIB004 </s> Physical exercise, inflammatory process and adaptive condition: an overview <s> ACUTe PhAse ResPONse (APR) <s> An athlete who trains intensely, yet consistently underperforms, ::: is considered to be suffering from overtraining syndrome ::: (OTS). OTS is a complex state that involves a large variety ::: of signs and symptoms. Symptoms include changes in mood ::: or behaviour, decreases or increases in concentration of different ::: blood molecules, and alterations in immune function. Although ::: several hypotheses have been proposed, each only explains a selective ::: aspect of OTS. Presently, the sole agreement is that OTS ::: is associated with excessive training and insufficient rest and ::: recovery. The hypothesis proposed in this paper suggests that ::: excessive training/competing causes repetitive tissue trauma, either ::: to muscle and/or connective tissue and/or to bony structures, ::: and that this results in chronic inflammation. It is further ::: proposed that traumatized tissue synthesizes a group of inflammatory ::: molecules, cytokines. Cytokines have been shown to coordinate ::: the different systems of the body to promote recovery. ::: Suggestions are made to detect, prevent, and rehabilitate the ::: overtrained athlete. <s> BIB005 </s> Physical exercise, inflammatory process and adaptive condition: an overview <s> ACUTe PhAse ResPONse (APR) <s> A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. <s> BIB006 </s> Physical exercise, inflammatory process and adaptive condition: an overview <s> ACUTe PhAse ResPONse (APR) <s> The current schedule of the Brazilian Soccer Championship may not give players enough recovery time between games. This could increase the chances of muscle damage and impaired performance. We hypothesized that plasma creatine kinase (CK) activity could be a reliable indirect marker of muscle overload in soccer players, so we sought to identify the reference values for upper limits of CK activity during a real-life elite competition. This study analyzed changes in plasma CK activity in 128 professional soccer players at different times during the Brazilian Championship. The upper limits of the 97.5th and 90th percentiles determined for CK activity were 1.338U/L and 975U/L, respectively, markedly higher than values previously reported in the literature. We also evaluated a team monthly throughout the Championship. The upper limit of the 90th percentile, 975U/L, was taken as the decision limit. Six players showing plasma CK values higher than this were asked to decrease their training for 1 week. These players presented lower CK values afterwards. Only one player with a CK value higher than the decision limit (1800U/L 1 day before a game) played on the field and was unfortunately injured during the game. The CK activity in all the other players showed a significant decrease over the course of the Championship, and the values became more homogeneous at the end. The results presented here suggest that plasma CK upper limit values can be used as a practical alternative for early detection of muscle overload in competing soccer players. <s> BIB007
An important point to be considered in relation to the inflammatory process is that the local response, described above, is usually followed by a systemic response, known as acute phase response BIB007 . The aim of the acute phase response is to adjust homeostasis for tissue repair. That is, within a few hours after the activation of the local inflammation, body can show a variety of physiological and behavioral systemic changes (also known as Sickness Behavior), which depend mainly on intensity and duration of the stress stimulus BIB006 . Some of them are presented in Picture 1. One of the most important responses of the acute phase involves an increase in the hepatic synthesis, with consequent increase in blood flow, the so-called acute phase proteins BIB005 . Among these, C-reactive protein (CRP), a-1-acid glycoprotein, serum amyloid A a-2-microglobulin, haptoglobin, fibrinogen, transferrin and ceruloplasmin, stand out BIB004 BIB001 . Each of these proteins has specific functions in the inflammatory context. On the other hand, there are some proteins that have decreased concentration in the acute phase in order to provide substrates for positive acute phase proteins. They are called negative acute phase proteins. Among them, albumin stands out BIB004 . In humans, studies classify positive acute phase proteins according to their potential to increase in the bloodstream during the acute phase (Picture 2) or, according to proteins that signal their hepatic synthesis within this phase (Picture 3). Positive acute phase proteins help holding the amplification of potentially lethal inflammation in various ways: by activating the complement system, action of proteases, removal of microorganisms and cellular metabolites, cellular remodeling, control of the gene expression, antithrombotic and hemostasis control, and control of the respiratory burst triggered by inflammatory cells and proteolytic enzymes, and activation of the local inflammation BIB004 BIB001  . In addition, some of them scavenge reactive ions (Fe +2 , Cu + ) and ROS BIB004  , thus modulating the inflammatory response. As an example, increased serum transferrin concentration has the function of holding secondary injuries to those generated by tissue injury via decrease in the plasma concentration of iron ion, which can participate in the generation of powerful cellular oxidants BIB004 . Regarding negative acute phase proteins, e.g., albumin, its decrease in plasma appears to occur due to a hepatic inhibition on the synthesis of its mRNA, mediated by other proteins related to inflammation such as IL-6, or due to the need of liver to increase the synthesis of positive acute phase proteins, requiring for this, a greater availability of amino acids obtained by the greater deterioration of albumin BIB002 . Also, an increased vascular permeability during the activation of the inflammatory process could trigger a greater efflux of albumin from plasma into the cell interstitium, causing the drop of its plasma concentration, thus contributing to the development of tissue edema, a peculiar feature of the inflammatory response BIB003 . Other compounds that have their plasma concentrations decreased during the acute phase are zinc and calcium BIB004 .