Leucocytes, cytokines and satellite cells : what role do they play in muscle damage and regeneration following eccentric exercise?

Exercise-induced muscle damage is an important topic in exercise physiology. However several aspects of our understanding of how muscles respond to highly stressful exercise remain unclear In the first section of this review we address the evidence that exercise can cause muscle damage and inflammation in otherwise healthy human skeletal muscles. We approach this concept by comparing changes in muscle function (i.e., the force-generating capacity) with the degree of leucocyte accumulation in muscle following exercise. In the second section, we explore the cytokine response to 'muscle-damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role of the cyclooxygenase enzymes (COX1 and 2). In summary, we propose that muscle damage as evaluated by changes in muscle function is related to leucocyte accumulation in the exercised muscles. 'Extreme' exercise protocols, encompassing unaccustomed maximal eccentric exercise across a large range of motion, generally inflict severe muscle damage, inflammation and prolonged recovery (> 1 week). By contrast, exercise resembling regular athletic training (resistance exercise and downhill running) typically causes mild muscle damage (myofibrillar disruptions) and full recovery normally occurs within a few days. Large variation in individual responses to a given exercise should, however be expected. The link between cytokine and satellite cell responses and exercise-induced muscle damage is not so clear The systemic cytokine response may be linked more closely to the metabolic demands of exercise rather than muscle damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to regeneration, whereas the biological significance of satellite cell proliferation after mild damage or non-damaging exercise remains uncertain. The COX enzymes regulate satellite cell activity, as demonstrated in animal models; however the roles of the COX enzymes in human skeletal muscle need further investigation. We suggest using the term 'muscle damage' with care. Comparisons between studies and individuals must consider changes in and recovery of muscle force-generating capacity.

Solutions for the flow of a micropolar fluid in a porous channel

How various additives can increase some cardio-vascular diseases and effects of transport for albumin and glucose through permeable membranes are some important studies in biomechanics. The rolling phenomena of the leucocytes gives rise to an inflammatory reaction along a vascular wall. Initiated by Eringen [5], a micropolar fluid is a satisfactory model for flows of fluids which contain micro-constituents which can undergo rotation.

A review of the economic consequences of a policy of universal leucodepletion as compared to existing practices

Leucodepletion, the removal of leucocytes from blood products improves the safety of blood transfusion by reducing adverse events associated with the incidental non-therapeutic transfusion of leucocytes. Leucodepletion has been shown to have clinical benefit for immuno-suppressed patients who require transfusion. The selective leucodepletion of blood products by bed side filtration for these patients has been widely practiced. This study investigated the economic consequences in Queensland of moving from a policy of selective leucodepletion to one of universal leucodepletion, that is providing all transfused patients with blood products leucodepleted during the manufacturing process. Using an analytic decision model a cost-effectiveness analysis was conducted. An ICER of $16.3M per life year gained was derived. Sensitivity analysis found this result to be robust to uncertainty in the parameters used in the model. This result argues against moving to a policy of universal leucodepletion. However during the course of the study the policy decision for universal leucodepletion was made and implemented in Queensland in October 2008. This study has concluded that cost-effectiveness is not an influential factor in policy decisions regarding quality and safety initiatives in the Australian blood sector.

Carbohydrate gel ingestion and immunoendocrine responses to cycling in temperate and hot conditions

PURPOSE: Heat stress might attenuate the effects of carbohydrate on immunoendocrine responses to exercise by increasing endogenous glucose production and reducing the rate of exogenous carbohydrate oxidation. The authors compared the efficacy of carbohydrate consumption on immune responses to exercise in temperate vs. hot conditions. METHODS: Ten male cyclists exercised on 2 separate occasions in temperate (18.1 +/- 0.4 degrees C, 58% +/- 8% relative humidity) and on another 2 occasions in hot conditions (32.2 +/- 0.7 degrees C, 55% +/- 2% relative humidity). On each occasion, the cyclists exercised in a fed state for 90 min at approximately 60% VO2max and then completed a 16.1-km time trial. Every 15 min during the first 90 min of exercise, they consumed 0.24 g/kg body mass of a carbohydrate or placebo gel. RESULTS: Neutrophil counts increased during exercise in all trials (p < .05) and were significantly lower (40%, p = .006) after the carbohydrate than after the placebo trial in 32 degrees C. The concentrations of serum interleukin (IL)-6, IL-8, and IL-10 and plasma granulocyte-colony-stimulating factor, myeloperoxidase, and calprotectin also increased during exercise in all trials but did not differ significantly between the carbohydrate and placebo trials. Plasma norepinephrine concentration increased during exercise in all trials and was significantly higher (50%, p = .01) after the carbohydrate vs. the placebo trial in 32 degrees C. CONCLUSION: Carbohydrate ingestion attenuated neutrophil counts during exercise in hot conditions, whereas it had no effect on any other immune variables in either temperate or hot conditions.

Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses

Lamellar pathology in experimentally-induced equine laminitis associated with euglycaemic hyperinsulinaemia is substantial by the acute, clinical phase (∼48 h post-induction). However, lamellar pathology of the developmental, pre-clinical phase requires evaluation. The aim of this study was to analyse lamellar lesions both qualitatively and quantitatively, 6, 12 and 24 h after the commencement of hyperinsulinaemia. Histological and histomorphometrical analyses of lamellar pathology at each time-point included assessment of lamellar length and width, epidermal cell proliferation and death, basement membrane (BM) pathology and leucocyte infiltration. Archived lamellar tissue from control horses and those with acute, insulin-induced laminitis (48 h) was also assessed for cellular proliferative activity by counting the number of cells showing positive nuclear immuno labelling for TPX2. Decreased secondary epidermal lamellar (SEL) width and increased histomorphological evidence of SEL epidermal basal (and supra-basal) cell death occurred early in disease progression (6 h). Increased cellular proliferation in SELs, infiltration of the dermis with small numbers of leucocytes and BM damage occurred later (24 and 48 h). Some lesions, such as narrowing of the SELs, were progressive over this time period (6–48 h). Cellular pathology preceded leucocyte infiltration and BM pathology, indicating that the latter changes may be secondary or downstream events in hyperinsulinaemic laminitis.

Inflammation in lung carcinogenesis

It was Dvorak in 1986 that postulated 'tumours are wounds that do not heal' as they share common cellular and molecular mechanisms, which are active in both wounds and in cancer tissue. Inflammation is a crucial part of the innate immune system that protects against pathogens and initiates adaptive immunity. Acute inflammation is usually a rapid and self-limiting process, however it does not always resolve. This leads to the establishment of a chronic inflammatory state and provides the perfect environment for carcinogenesis. Inflammation and cancer have long had an association, going back as far as Virchow in 1863, when leucocytes were noted in neoplastic tissue. It has been estimated that approximately 25% of all malignancies are initiated or exacerbated by inflammation caused by infectious agents. Furthermore, inflammation is linked to all of the six hallmarks of cancer (evasion of apoptosis, insensitivity to anti-growth signals, unlimited replicative potential, angiogenesis, increase in survival factors and invasion and metastasis). It is thought that inflammation may play a critical role in lung carcinogenesis given that individuals with inflammatory lung conditions have an increased risk of lung cancer development. Cigarette smoking can also induce inflammation in the lung and smokers are at a higher risk of developing lung cancer than non-smokers. However, exposure to a number of environmental agents such as radon, have also been demonstrated as a causative factor in this disease. This chapter will focus on inflammation as a contributory factor in non small cell lung cancer (NSCLC), concentrating primarily on the pathological involvement of the pro-inflammatory cytokines, TNF-α, IL-1β, and the CXC (ELR+) chemokine family. Targeting of inflammatory mediators will also be discussed as a therapeutic strategy in this disease. © 2013 by Nova Science Publishers, Inc. All rights reserved.

Ibuprofen ingestion does not affect markers of post-exercise muscle inflammation

Purpose: We investigated if oral ingestion of ibuprofen influenced leucocyte recruitment and infiltration following an acute bout of traditional resistance exercise Methods: Sixteen male subjects were divided into two groups that received the maximum over-the-counter dose of ibuprofen (1200mg d−1) or a similarly administered placebo following lower body resistance exercise. Muscle biopsies were taken from m.vastus lateralis and blood serum samples were obtained before and immediately after exercise, and at 3 and 24 h after exercise. Muscle cross-sections were stained with antibodies against neutrophils (CD66b and MPO) and macrophages (CD68). Muscle damage was assessed via creatine kinase and myoglobin in blood serum samples, and muscle soreness was rated on a ten-point pain scale. Results: The resistance exercise protocol stimulated a significant increase in the number of CD66b+ and MPO+ cells when measured 3 h post exercise. Serum creatine kinase, myoglobin and subjective muscle soreness all increased post-exercise. Muscle leucocyte infiltration, creatine kinase, myoglobin and subjective muscle soreness were unaffected by ibuprofen treatment when compared to placebo. There was also no association between increases in inflammatory leucocytes and any other marker of cellular muscle damage. Conclusion: Ibuprofen administration had no effect on the accumulation of neutrophils, markers of muscle damage or muscle soreness during the first 24 h of post-exercise muscle recovery.