Photoinduced reactivity of titanium dioxide

Immunometabolism is emerging an important area of immunological research, but for many immunologists the complexity of the field can be daunting. Here, the authors provide an overview of six key metabolic pathways that occur in immune cells and explain what is known (and what is still to be uncovered) concerning their effects on immune cell function. In recent years a substantial number of findings have been made in the area of immunometabolism, by which we mean the changes in intracellular metabolic pathways in immune cells that alter their function. Here, we provide a brief refresher course on six of the major metabolic pathways involved (specifically, glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism), giving specific examples of how precise changes in the metabolites of these pathways shape the immune cell response. What is emerging is a complex interplay between metabolic reprogramming and immunity, which is providing an extra dimension to our understanding of the immune system in health and disease.

A guide to immunometabolism for immunologists

Stress-induced immunological reactions to exercise have stimulated much research into stress immunology and neuroimmunology. It is suggested that exercise can be employed as a model of temporary immunosuppression that occurs after severe physical stress. The exercise-stress model can be easily manipulated experimentally and allows for the study of interactions between the nervous, the endocrine, and the immune systems. This review focuses on mechanisms underlying exercise-induced immune changes such as neuroendocrinological factors including catecholamines, growth hormone, cortisol, β-endorphin, and sex steroids. The contribution of a metabolic link between skeletal muscles and the lymphoid system is also reviewed. The mechanisms of exercise-associated muscle damage and the initiation of the inflammatory cytokine cascade are discussed. Given that exercise modulates the immune system in healthy individuals, considerations of the clinical ramifications of exercise in the prevention of diseases for which the...

Exercise and the Immune System: Regulation, Integration, and Adaptation

https://www.cell.com/trends/biochemical-sciences/pdf/S0968-0004(10)00091-5.pdf

Glutamine addiction: a new therapeutic target in cancer.

The resurgence of research into cancer metabolism has recently broadened interests beyond glucose and the Warburg effect to other nutrients, including glutamine. Because oncogenic alterations of metabolism render cancer cells addicted to nutrients, pathways involved in glycolysis or glutaminolysis could be exploited for therapeutic purposes. In this Review, we provide an updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo, and explore the recent potential applications of basic science discoveries in the clinical setting.

/pdf/from-krebs-to-clinic-glutamine-metabolism-to-cancer-therapy-4hqfit9bso.pdf

From Krebs to clinic: glutamine metabolism to cancer therapy.

Overtraining appears to be caused by too much high intensity training and/or too little regeneration (recovery) time often combined with other training and nontraining stressors. There are a multitude of symptoms of overtraining, the expression of which vary depending upon the athlete's physical and physiological makeup, type of exercise undertaken and other factors. The aetiology of overtraining may therefore be different in different people suggesting the need to be aware of a wide variety of parameters as markers of overtraining. At present there is no one single diagnostic test that can define overtraining. The recognition of overtraining requires the identification of stress indicators which do not return to baseline following a period of regeneration. Possible indicators include an imbalance of the neuroendocrine system, suppression of the immune system, indicators of muscle damage, depressed muscle glycogen reserves, deteriorating aerobic, ventilatory and cardiac efficiency, a depressed psychological profile, and poor performance in sport specific tests, e.g. time trials. Screening for changes in parameters indicative of overtraining needs to be a routine component of the training programme and must be incorporated into the programme in such a way that the short term fatigue associated with overload training is not confused with the chronic fatigue characteristic of overtraining. An in-depth knowledge of periodisation of training theory may be necessary to promote optimal performance improvements, prevent overtraining, and develop a system for incorporating a screening system into the training programme. Screening for overtraining and performance improvements must occur at the culmination of regeneration periods.

Overtraining in athletes. An update.

A growing number of reports have become available which implicate infectious disease with reduced performance in athletes. The immune system consists of both nonspecific and specific components geared to control infections. Adaptive immunity functions through both antibody-mediated and cell-mediated compartments to establish and maintain long term immunity to infectious agents. Evidence is accumulating to support the view that physical exercise can lead to modification of the cells of the immune system. However, studies have often not been well designed to control exercise protocols when examining the effects of exercise on the immune system. Large numbers of peripheral blood lymphocytes are mobilised with exercise and in vitro tests indicate that temporarily these cells may not be capable of responding normally to mitogens. These reactions appear to be influenced by hormones to some degree and there are reports that the cells of the immune system are extremely active biochemically and may depend on products from muscles to maintain their activity. Specific populations within the circulating leucocyte pool vary significantly with exercise and there is some evidence that the T4/T8 lymphocyte ratio may become significantly reduced. This reduction in ratio may be related to the variable responses to T and B cell mitogens recorded in vitro which overall suggests that a temporary immune suppression may exist following certain training or performance schedules. It is argued that this may lead to a temporary susceptibility to infection and could result from overtraining.

Exercise and the Immune Response

Attention is drawn to the long-term effects of atmospheric contaminants in general (and cigarette smoke in particular) on immunological control mechanisms that are accepted as playing a vital role in the maintenance of health. The review argues that a hostile environment within the respiratory tract created by inhalation of air contaminants compromises local immunological function in the short term, and ultimately depresses systemic immunological function. Whether such a decline in immunological homeostasis is due directly to toxicity, or indirectly to accelerated aging of susceptible elements of the immune system, is speculative. The changes observed in both man and experimental animals exposed for long periods to air contaminants in many respects parallel those associated with normal aging and may represent an acceleration of the process of senescence. Specific biological effects of smoking, air pollution and immune functions in man and animal models are reviewed. The precise mechanism(s) by which air contaminants affect immunological function remains speculative, but the relative resistance of specified-pathogen-free animals to these agents infers a central role for the hosts' normal bacterial flora in the process.

https://mmbr.asm.org/content/mmbr/41/1/205.full.pdf

Environmentally induced changes in immunological function: acute and chronic effects of inhalation of tobacco smoke and other atmospheric contaminants in man and experimental animals.

The effects of glutamine concentration on the phagocytosis of an opsonized antigen, the synthesis of RNA, and the production of interleukin-1 (IL-1) by macrophages were investigated in vitro. A minimum A minimum of 0.125 mmol/L glutamine was required for a significant increase in phagocytosis of opsonized sheep erythrocytes, compared with that recorded for macrophages cultured in the absence of glutamine. The synthesis of 3H-RNA by macrophages also required 0.125 mmol/L glutamine in the culture medium before it was significantly increased above the levels of control cultures. A minimum of 0.03 mmol/L glutamine was required for the induction of significant levels of IL-1 by lipopolysaccharide (LPS)-stimulated macrophages. Therefore, recent findings suggesting that decreases in plasma glutamine resulting from major burn injury, sepsis, trauma, and surgery may be partly responsible for the associated impairment of immune function now have a basis in both phagocytosis and in modulation of the synthesis of IL-1 (the first cytokine of the interleukin cascade that leads to specific immunity) by macrophages, in addition to the previously established dependency of lymphocytes on external sources of glutamine for their replication.

Glutamine and macrophage function.

A number of studies have demonstrated considerable plasma volume changes during and after exposure to different environmental and physiological conditions. These changes are thought to result from transient fluid shifts into (haemodilution) and out of (haemoconcentration) the intravascular space. If the levels of plasma constituents are to be routinely measured for research purposes or used as indicators of training adaptation or the health of an athlete, then it is important to consider the dynamic nature of plasma volume. Controversy still exists over the relevance of plasma volume interactions with plasma constituent levels, and while some investigators have taken plasma volume shifts into account, others have chosen to ignore these changes. Bouts of acute exercise have been shown to produce a transient haemoconcentration immediately after long distance running, bicycle ergometry and both maximal and submaximal swimming exercise. While these changes are transient, lasting only a few hours, other studies have reported a longer term haemodilution following acute exercise. In addition, endurance training has been shown to cause long term expansion of the plasma volume. It would, therefore, seem important to consider the influence of plasma volume changes on plasma solutes routinely measured for research, and as markers of training adaptation, prior to arriving at conclusions and recommendations based purely on their measured plasma level. To further confound this issue, plasma volume changes are known to be associated with heat acclimatisation, hydration state, physical training and postural changes, all of which may differ from one experiment or exercise bout to the next, and should thus be taken into account.

The influence of exercise-induced plasma volume changes on the interpretation of biochemical parameters used for monitoring exercise, training and sport.

David Keast

Papers

Overtraining in athletes. An update.

Exercise and the Immune Response

Environmentally induced changes in immunological function: acute and chronic effects of inhalation of tobacco smoke and other atmospheric contaminants in man and experimental animals.

Glutamine and macrophage function.

The influence of exercise-induced plasma volume changes on the interpretation of biochemical parameters used for monitoring exercise, training and sport.