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Cytokine Changes following Acute Ethanol Intoxication in Healthy Men: A Crossover Study.
Neupane, SP, Skulberg, A, Skulberg, KR, Aass, HC, Bramness, JG
Mediators of inflammation. 2016;:3758590
Abstract
Alcohol is a known modulator of the innate immune system. Owing to the absence of human studies, alcohol's effect on circulating cytokine profile remains unclear. We investigated the effect of acute high dose alcohol consumption on systemic cytokine release. After an overnight fasting, alcohol-experienced healthy male volunteers (N = 20) aged 25-45 years were given oral ethanol in the form of vodka (4.28 mL/kg) which they drank over a period of 30 minutes reaching peak blood alcohol concentration of 0.12% (SD 0.028). Blood samples were obtained prior to alcohol intake as well as 2, 7, and 12 hours thereafter. Serum levels of the inflammatory cytokines IL-1β, IL-1Ra, IL-6, IL-10, IL-17, IFN-γ, MCP-1, and TNF-α were determined by the multibead-based assay. Baseline cytokine levels were not related to BMI, hepatic parameters, electrolytes, glucose, or morning cortisol levels. Within 2 hours of alcohol intake, levels of IL-1Ra were elevated and remained so throughout the assessment period (p for trend = 0.015). In contrast, the levels of the chemokine MCP-1 dropped acutely followed by steadily increasing levels during the observation period (p < 0.001). The impact of sustained elevated levels of MCP-1 even after the clearance of blood alcohol content deserves attention.
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Intervention at the level of the neuroendocrine-immune axis and postoperative pneumonia rate in long-term alcoholics.
Spies, C, Eggers, V, Szabo, G, Lau, A, von Dossow, V, Schoenfeld, H, Althoff, H, Hegenscheid, K, Bohm, B, Schroeder, T, et al
American journal of respiratory and critical care medicine. 2006;(4):408-14
Abstract
RATIONALE Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity. OBJECTIVES The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients. METHODS In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence. Nonalcoholic patients were included but only as a descriptive control. Perioperative intervention with low-dose ethanol (0.5 g/kg body weight per day), morphine (15 mug/kg body weight per hour), ketoconazole (200 mg four times daily), and placebo was started on the morning before surgery and continued for 3 d after surgery. Blood samples to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1, 3, and 7 after surgery. MEASUREMENTS AND MAIN RESULTS In long-term alcoholic patients, all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio. All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened intensive care unit stay by 9 d (median) compared with the placebo-treated long-term alcoholic patients. CONCLUSIONS Intervention at the level of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients.
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Recent insights into the role of the innate immune system in the development of alcoholic liver disease.
Nagy, LE
Experimental biology and medicine (Maywood, N.J.). 2003;(8):882-90
Abstract
The innate immune system is responsible for the rapid, initial response of the organism to potentially dangerous stresses, including pathogens, tissue injury, and malignancy. Pattern-recognition receptors of the toll-like receptor (TLR) family expressed by macrophages provide a first line of defense against microbial invasion. Activation of these receptors results in a stimulus-specific expression of genes required to control the infection, including the production of inflammatory cytokines and chemokines, followed by the recruitment of neutrophils to the site of infection. The early stages in the development of alcoholic liver disease (ALD) follow a pattern characteristic of an innate immune response. Kupffer cells, the resident macrophages in the liver, are activated in response to bacterial endotoxins (lipopolysaccharide, LPS), leading to the production of inflammatory and fibrogenic cytokines, reactive oxygen species, as well as the recruitment of neutrophils to the liver. One mechanism by which chronic ethanol can turn the highly regulated innate immune response into a pathway of disease is by disrupting the signal transduction cascades mediating the innate immune response. Recent studies have identified specific modules in the TLR-4 signaling cascade that are disrupted after chronic ethanol exposure, including CD14 and the mitogen-activated protein kinase family members, ERK1/2 and p38. Enhanced activation of these TLR-4 dependent signaling pathways after chronic ethanol likely contributes to the development of alcoholic liver disease.
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Acute intake of moderate amounts of red wine or alcohol has no effect on the immune system of healthy men.
Watzl, B, Bub, A, Briviba, K, Rechkemmer, G
European journal of nutrition. 2002;(6):264-70
Abstract
BACKGROUND A recent prospective cohort study revealed that moderate wine consumption but not consumption of other alcoholic beverages is associated with a decreased risk of common cold. In contrast, wine constituents such as ethanol and polyphenols are known to suppress immunity. AIM OF THE STUDY We investigated whether acute intake of a moderate amount of alcohol modulates immune functions in healthy men and whether polyphenols in red wine with antioxidative and immunomodulatory potential induce changes in immune functions that differ from those induced by the consumption of the 12 % ethanol. METHODS Six healthy males with moderate alcohol consumption patterns randomly consumed a single dose of 500 ml of red wine (12 % ethanol), a 12 % ethanol dilution, dealcoholized red wine, and red grape juice, respectively. The following immune functions were measured before beverage consumption and 1, 3, and 24 h later: phagocytic activity and intensity of neutrophils and monocytes, production of tumor necrosis factor-alpha, interleukin-2, and interleukin-4, lymphocyte proliferation, and lytic activity of natural killer cells. RESULTS Acute consumption of a moderate amount of red wine and of a 12 % ethanol solution had no effect on immune functions in men. Acute consumption of polyphenol-rich beverages (dealcoholized red wine and red grape juice) also did not affect immunity. CONCLUSIONS This study clearly shows that moderate consumption of alcohol at doses which inversely correlate with cardiovascular disease risk has no short-term effect on human immune cell functions. Acute intake of polyphenol-rich beverages such as red grape juice and dealcoholized red wine also does not affect immunity.
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Preoperative nutritional support at home in head and neck cancer patients: from nutritional benefits to the prevention of the alcohol withdrawal syndrome.
Bertrand, PC, Piquet, MA, Bordier, I, Monnier, P, Roulet, M
Current opinion in clinical nutrition and metabolic care. 2002;(4):435-40
Abstract
PURPOSE OF REVIEW Preoperative nutritional support in severely malnourished patients decreases complications after major surgery. This review summarizes previous studies on head and neck cancer patients undergoing surgery, and offers recommendations on preoperative nutritional support based on the literature and our experience. RECENT FINDINGS Head and neck cancer has a large impact on the patient's quality of life and a high mortality rate. Aggressive surgical resection followed by soft-tissue and osseous reconstruction is the gold standard of treatment. The incidence of postoperative complications is high at 20-50%. Malnutrition and alcohol withdrawal syndrome are often present, and are considered risk factors for developing wound infection after head and neck cancer surgery. Proactive intervention by preoperative nutritional support may correct nutrient deficiencies, minimize malnutrition-related morbidity and mortality, reduce the length and cost of hospitalization, and may prevent alcohol withdrawal syndrome. Nutritional support given preoperatively for 7-10 days decreases postoperative complications by approximately 10% in malnourished patients with weight loss of 10% or more. Oral liquid supplements and enteral nutrition are useful to support head and neck cancer patients preoperatively. Enteral nutrition is safer, more physiological, less expensive and practicable at home compared with parenteral nutrition, which is not usually indicated in these patients. SUMMARY Enteral nutrition is efficient in preoperative phase to prevent postoperative complications. However evidence is insufficient to conclude that preoperative immune-enhancing enteral feeding provides any supplementary benefit by comparison with a standard diet. Our experience with the preoperative approach in head and neck cancer patients is reported in this paper.