The Antioxidant, Anti-Inflammatory and Immunomodulatory Effects of Camel Milk.

Camel milk (CM) has been found to have several health benefits, including antiviral, antibacterial, anti-tumor, anti-fungal, antioxidant, hypoglycaemic and anti-cancer activities. In addition, CM can counter signs of aging and may be a useful naturopathic treatment for autoimmune diseases. The composition of CM varies with geographic origin, feeding conditions, seasonal and physiological changes, genetics and camel health status. In the present review, we collate the diverse scientific literature studying antioxidant, anti-inflammatory and immunomodulatory effects of CM and its bioactive compounds. The databases Scopus, PubMed, and Web of Science were searched until the end of September 2021 using the keywords: camel milk, antioxidant, anti-inflammatory, immunomodulatory. The anti-inflammatory mechanism of CM in various inflammatory disorders was consistently reported to be through modulating inflammatory cells and mediators. The common anti-inflammatory bioactive components of CM seem to be lactoferrin. The antioxidant effects of α-lactalbumin, ß-caseins and vitamin C of CM work by reducing or inhibiting the production of reactive oxygen species (ROS), hydroxyl radicals, nitric oxide (NO), superoxide anions and peroxyl radicals, likely alleviating oxidative stress. Higher levels of protective proteins such as lysozyme, IgG and secretory IgA compared to cow's milk, and insulin-like protein activity of CM on ß cells appear to be responsible for the immunomodulatory properties of CM. The evidence indicates that CM and its bioactive components has the potential to be a therapeutic value for diseases that are caused by inflammation, oxidative stress and/or immune-dysregulation.

Hydroalcoholic extract of dill and aerobic training prevents high-fat diet-induced metabolic risk factors by improving miR-33 and miR-223 expression in rat liver.

Exercise training and medicinal herb supplementation may improve microRNAs (miRNAs) expression associated with obesity. This study aimed to assess the effects of 10 weeks of aerobic training (AT) and dill extract (DE) on miR-33 and miR-223 expression of liver in high-fat diet (HFD)-induced obese rats. Forty male Wistar rats were fed a defined high-fat (n = 32) and standard (n = 8, nonobese control [NC]) diet. After obesity induction, obese rats were randomly allocated to four groups: AT, DE, AT + DE, and obese control (OC). Rats were euthanized and plasma and liver tissue samples were collected after the intervention. The liver expression of miR-33 was lower in the AT, DE, AT + DE, and NC groups compared with the OC group. Also, the liver miR-223 expression was higher in the AT, DE, AT + DE, and NC groups compared with the OC group. Moreover, the liver expression of miR-223 in the AT + DE group was higher compared with the AT and DE groups. The AT, DE, AT + DE, and NC groups had lower liver TC compared with the OC group. Also, the plasma level of apolipoprotein B (Apo B) was significantly lower, and liver HDL-C was significantly higher in the AT + DE and NC groups compared with the OC group. These findings show that long-term AT combined with the intake of DE may improve the plasma levels of Apo B, and TC and HDL-C levels in the liver, which is probably due to AT and DE positive effects on miR-33 and miR-223 in the liver of obese rats. PRACTICAL APPLICATIONS: Aerobic training reduces overweight and obesity health problems, however, the duration and intensity of the exercise training distinguish between individuals. We used an integrated approach combining pharmacological and non-pharmacological as a medical strategy to prevent HFD-induced metabolic injury in obese rats. The present results discovered that a combination of AT + DE intervention improves the miR-33 and miR-223 in the liver of obese rats.

Influence of Eimeria spp. infection and dietary inclusion of arginine on intestine histological parameters, serum amino acid profile and ileal amino acids digestibility in broiler chicks.

Coccidiosis is considered to be one of the most important challenge in the poultry industry causes economic losses due to the destruction in the digestive tract of chicken. It disturbs amino acids profile and their digestibility, leading to weight lost and economic burden. Using dietary arginine may decrease the adverse effects of coccidiosis on chicken digestive tract. This study aimed to evaluate the effects of dietary inclusion of arginine on intestine histological parameters, serum amino acid concentration and ileal amino acid digestibility of broiler chicks infected with coccidiosis. A total number of 384 one-d-old broiler chicks (Ross 308) of mixed sex with initial weight of 42 ±â€¯2 g was allocated into 8 groups with 8 birds/pen from grower period. At 21 days of age, broiler chicks were infected with a mixture of Eimeria spp. Broiler chicks were divided into infected and un-infected groups and received arginine at recommended levels of 85, 100, 125 and 150 %. Intestinal morphology and lesions, serum amino acid concentration and ileal amino acid digestibility were evaluated. Broiler chicks infected with Eimeria spp. showed lower villus height and villus height: crypt depth ratio and also higher intestinal lesions (P < 0.05). Coccidia infection decreased the ileal amino acid digestibility for all studied amino acids and also reduced serum concentrations of amino acids, except lysine and isoleucine (P < 0.05). Dietary supplementation of arginine especially in higher levels significantly increased villus height and villus height:crypt depth ratio and decreased lesions (P < 0.05). Moreover, dietary supplementing of arginine increased the serum concentration of arginine (P < 0.05), but it did not have any significant effect on its digestibility (P > 0.05). In sum, coccidiosis decreases amino acid digestibility and serum amino acid concentration, but dietary inclusion of higher levels of arginine significantly improved histological parameters of broiler chicks infected with coccidiosis.

Effect of Training with or without Ziziphus Jujuba Extract on Cardiokines in Heart Tissue of Myocardial Infarcted Rats.

BACKGROUND: Today, the importance of physical activity as a preventative way for cardiovascular disease has attracted much attention.The aim of this study is to investigate the effect of 6 weeks of interval training with or without extract of Ziziphus jujuba on lipocalcin-2 (LCN2) and adiponectin levels in heart tissue in male Wistar rats with myocardial infarction. METHODS: Thirty male Wistar rats (mean weight, 180-220 g and age, 2-3 months) were divided into five groups, including (1) Healthy control; (2) Isoprenaline-treated group (ISO); (3) ISO + jujube extracts (JE); (4) Trained ISO rats; and (5) Trained ISO rats + JE. Exercise was performed (5 days/week, for 6 week including 54-min cycles with speed of 23 m/min and 54-min cycles with speed of 15 m/min). After 48 h of the last training session, the rats were sacrificed, and their heart tissue was excised. The significant level of statistical data was analyzed by one-way ANOVA test. RESULTS: LCN2 levels significantly decreased in trained ISO rats + JE group after 6 weeks of interval training with JE consumption, compared to ISO group. However, the consumption of jujuba extracts with and without interval training did not show any significant changes in adiponectin levels of rat's heart tissue, compared to ISO (P < 0.05). CONCLUSIONS: Because the LCN2 inflammatory factor decreased after 6 weeks of exercise and consumption of the extract, it seems that performing interval training with JE consumption can be an effective method in the cardiac rehabilitation phase after a heart attack.

Antihyperglycemic and antihyperlipidemic activities of Nannochloropsis oculata microalgae in Streptozotocin-induced diabetic rats.

Background It is well documented that biologically active components of microalgae can be utilized for treatment of different diseases. This study was conducted to evaluate the antihyperglycemic and antihyperlipidemic activities and weight control of Nannochloropsis oculata microalgae (NOM) in Streptozotocin-induced diabetic male rats. Methods Diabetes was induced by intraperitoneal administration of Streptozotocin (55 mg/kg). Healthy and diabetic rats were divided in to six groups. Healthy and diabetic rats orally received distilled water or NOM (10 and 20 mg/kg) for three weeks. Results Oral administration of NOM to diabetic rats significantly reduced the serum concentrations of glucose, cholesterol, triglycerides, LDL and increased the serum concentration of insulin and HDL-C (P<0.05). Treatment with NOM had no significant effect on blood parameters in healthy rats (P>0.05). Also, NOM maintained body weight in diabetic rats (P<0.05). Conclusion It can be concluded that NOM has antihyperglycemic and antihyperlipidemic activities in diabetic rats.

The response of intercellular adhesion molecule-1 to exhaustive submaximal exercise and its correlation with physiological and anthropometric measures.

Introduction:Intercellular adhesion molecule-1 (ICAM-1) acts as the main factor in the occurrence of atherosclerosis and inflammatory diseases. This study aimed to investigate the response of ICAM-1to exhaustive submaximal exercise and its correlation with maximal oxygen consumption (VO2max), body mass index (BMI), waist-hip ratio (WHR), body fat percentage (BF %) and calories burned during exercise (CB) in healthy men. Materials and methods:Thirteen healthy men (mean ± standard deviation: age 23 ± 3 years, weight 78 ± 4 kg, height 180 ± 4 cm) cooperated in this quasi-experimental study and performed a single bout of exhaustive submaximal exercise on a cycle ergometer. Blood samples were collected from the antecubital vein before and immediately after exercise. Data were analyzed using the paired sample t-test and Pearson's correlation coefficient (α=0.05). Results:Exhaustive submaximal exercisehad no significant effect on serum sICAM-1. Also, there were no significant correlations between ICAM-1 induced by the exhaustive submaximal exercise and VO2max, BMI, WHR, BF % and CB. Conclusions:According to our findings, it cannot be ruled out that exhaustive submaximal exercise results in pathological and inflammatory conditions in healthy men. In Also, anthropometric and physiological parameters do not affect the response of ICAM-1 to exercise in healthy men.

Nanoselenium Supplementation of Heat-Stressed Broilers: Effects on Performance, Carcass Characteristics, Blood Metabolites, Immune Response, Antioxidant Status, and Jejunal Morphology.

An experiment was conducted to investigate the effects of dietary nanoselenium supplementation at 0, 0.6 and 1.2 mg/kg of diet on growth performance, serum biochemical parameters, immune response, antioxidant capacity, and jejunal morphology of 29-d-old male broilers subjected to heat stress at 37 ± 1°C for 14 d. Broilers were fed for 42 d on the experimental diets. The results showed that nanoselenium supplementation had no effect on growth performance, but it supplementation at the rate of 1.2 mg/kg diet decreased the serum concentration of cholesterol prior to the heat exposure. Further, dietary nanoselenium supplementation linearly increased the high-density lipoprotein cholesterol concentration, while linearly decreased those of low-density lipoprotein cholesterol and aspartate aminotransferase in the serum before applying heat stress. Compared with thermoneutral temperature, heat stress reduced body mass gain, feed intake, percentages of carcass, breast, leg, abdominal fat, bursa of Fabricius, thymus, antibody response against sheep red blood cells, serum concentration of protein, erythrocyte activities of glutathione peroxidase and superoxide dismutase, jejunal villus height, and villus height to crypt depth ratio, while increased feed conversion ratio, percentages of liver, gizzard, pancreas, gallbladder, heart, and the concentrations of aspartate aminotransferase and malondialdehyde. Dietary supplementation of nanoselenium linearly reduced the abdominal fat and liver percentages, while linearly increased the activity of glutathione peroxidase and villus height in heat-stressed broilers. Furthermore, the lower level of nanoselenium decreased the percentages of gizzard and heart in broilers under heat stress. The diet supplemented with 1.2 mg/kg nanoselenium improved feed conversion ratio and increased antibody response against sheep red blood cells, activity of superoxide dismutase, and villus height to crypt depth ratio, but decreased the serum concentrations of cholesterol, low-density lipoprotein cholesterol, and malondialdehyde in heat-stressed broilers. The results suggest that supplemental nanoselenium improved growth performance, internal organs health, immune response, and jejunal morphology by alleviating the oxidative stress induced by heat stress.

The effect of Prosopis farcta beans extract on blood biochemical parameters in streptozotocin-induced diabetic male rats.

BACKGROUND: The use of herbals in the treatment of diabetes mellitus is a well-established practice in traditional medicine. The medicinal plant Prosopis farcta has some antioxidant activity, which may be useful in diabetic patients. Since, there is no report on the antidiabetic effect of the P. farcta, this study evaluated antidiabetic activity of P. farcta bean extract (PFE) in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Hyperglycemia was induced in male albino Wistar rats by intraperitoneal injection of STZ (55 mg/kg body weight [BW]), after which, the animals were randomly allocated into six experimental groups as follows: Group 1: Normal rats (received normal saline), Groups 2 and 3: Normal rats received PFE; (50 and 75 mg/kg BW), Group 4: Diabetic control rats, Group 5: Diabetic rats received PFE (50 mg/kg BW), Group 6: Diabetic rats received PFE (75 mg/kg BW). Three days after induction of diabetes, rats were received an extract of PFE orally for 12 days. Blood samples were collected by cardiac puncture to determine liver enzymes; aspartate aminotransferase and alanine aminotransferase (AST and ALT), cholesterol, triglyceride (TG), high and low density lipoproteins (HDL and LDL). RESULTS: The administration of PFE (50 and 75 mg/kg) in STZ-induced diabetic rats significantly reduced the blood glucose levels when compared with the STZ-control group (227.2 ± 12.00 and 259.6 ± 7.03 vs. 454.6 ± 12.66, P < 0.001). PFE in diabetic groups had no significant effect on the levels of cholesterol, TG, HDL, LDL, AST, and ALT compare to the STZ-control group. CONCLUSION: P. farcta could reduce blood glucose in diabetic rats.

Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training.

AIM AND SCOPE: The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production induced by high-intensity interval training (HIIT). MATERIALS AND METHODS: In the present study, 24 rats were randomly divided into control (C), supplementation (S), HIIT, and HIIT + supplementation (HIIT+S) groups. HIIT training protocol on a treadmill (at a speed of 40-54 m/min) and vitamin E succinate supplementation (60 mg/kg/day) was conducted for 6 weeks. RESULTS: Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002). Also, serum TNF-α concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001) in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-α when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05). However, no significant changes were observed in serum TNF-α (P = 0.31) and IL-6 (P = 0.52) concentrations in the HIIT + S group compared with the C group. CONCLUSION: HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate.

Hepatoprotective Potential of Prosopis farcta Beans Extracts against Acetaminophen-induced Hepatotoxicity in Wister Rats.

BACKGROUND: Hepatotoxicity by acetaminophen is the most frequent cause of acute liver failure in many countries. Prosopis farcta beans extract (PFE) has some antioxidant property and may alleviate hepatotoxicity. Therefore, the aim of this study was to evaluate effects of PFE against acetaminophen-induced hepatotoxicity. METHODS: Thirty-six male Wistar albino rats weighing 220 ± 30 g were distributed into six groups. Two groups were pretreated with PFE (50 and 75 mg/kg) for 7 days before administration of acetaminophen (600 mg/kg). Two were given acetaminophen or PFE (50 and 75 mg/kg) alone, and the control received normal saline. One day after acetaminophen, administration blood samples were collected by cardiac puncture to determine liver function enzymes markers; aspartate aminotransferase and alanine aminotransferase (AST and ALT), cholesterol, triglyceride (TG), high, low, and very low density lipoproteins (LDL and VLDL). RESULTS: In acetaminophen-treated rat plasma AST (314 ± 18.54 vs. 126.37 ± 4.13), ALT (304 ± 49.24 vs. 187.33 ± 3.71), cholesterol, TG, LDL, and VLDL were increased by 149, 160, 37, 92, 60, and 94%, respectively. PFE at both doses significantly (P < 0.05) attenuated the above biochemical indices to near normal. CONCLUSIONS: Prosopis farcta beans extract (50 and 75 mg/kg) exhibited hepatoprotective activity against APAP.

Effects of milk thistle seed against aflatoxin B1 in broiler model.

BACKGROUND: Consumption of aflatoxin B1 (AFB1) contaminated products can pose a risk of development of various diseases in human and animals due to radical production. The scope of this work is to evaluate the efficacy of milk thistle seed (MTS), as a radical scavenger, on serum biochemistry, lipid profile and liver enzymes against AFB1 in broiler chickens contaminated with AFB1. MATERIALS AND METHODS: The effect of nine experimental treatments (3 × 3 factorial design) was assessed using 216 one-d-old Ross 308 male broiler chicks in a randomized complete design with four replicates of six birds for each dietary treatments: Control (T1), 250 ppb AFB1 (T2), 500 ppb AFB1 (T3), 0.5% MTS (T4), 0.5% MTS Plus 250 ppb AFB1 (T5), 0.5% MTS Plus 500 ppb AFB1 (T6), 1.0% MTS (T7), 1.0% MTS Plus 250 ppb AFB1 (T8), and 1.0% MTS Plus 500 ppb AFB1 (T9). The individual and combined effects of dietary AFB1 and MTS on serum biochemistry factors (Glucose, Calcium, Phosphorus, Iron, Creatinine, and Uric acid), lipid profile (Triglyceride, Cholesterol, Low density lipoprotein (LDL), and High density lipoprotein (HDL)) and liver enzymes aspartate amino-transferase and alanine amino-transaminase (ALT) in broilers were evaluated at 21 days of age. Also, statistical packages Macros-1.002 (2010) were used to perform the above analysis on computer. RESULTS: Consumption of 500 ppb AFB1 in to the diet significantly decreased HDL (58.13 ± 2.65), Calcium (7.11 ± 0.13), and Glucose (197.1 ± 7.42) compared to the control group (85.12 ± 1.95, 9.45 ± 0.17 and 223.1 ± 6.61, respectively), (P < 0.05). In contrast, it significantly increased creatinine (2.25 ± 0.011) and AST (244.51 ± 4.91). Using MTS together with AFB1 significantly reduced the effect of AFB1 on the above parameters. CONCLUSION: MTS can provide protection against the negative effects of AFB1 on broiler chicks.

IL-8 production by macrophages is synergistically enhanced when cigarette smoke is combined with TNF-alpha.

Macrophages are key inflammatory cells in chronic obstructive pulmonary disease (COPD). The pathophysiology of cigarette smoke-induced lung emphysema is complex but there is a clear role for reactive oxygen species (ROS, such as peroxynitrite), tumor necrosis factor (TNF-alpha) and interleukin (IL)-8. We investigated whether TNF-alpha or cigarette smoke medium (CSM) alone or in combination induces the production of IL-8 by human macrophages or monocyte lymphoma U937. CSM and TNF-alpha induce a dose- and time-dependent increase in IL-8 production. Interestingly, when sub-threshold concentrations of CSM and TNF-alpha were co-incubated, a 1500% increase in IL-8 production was observed compared to either of the compounds alone. Similar results were obtained with TNF-alpha and the peroxynitrite donor SIN-1. Moreover, the overproduction of IL-8 was associated with an enhanced increase in the translocation of NF-kappaB and an enhanced decrease in glutathione levels. Preincubation of the cells with antioxidants, such as N-acetyl-L-cysteine (NAC), prevented the overproduction of IL-8 and activation of NF-kappaB. In conclusion, CSM exposure of macrophages up-regulates the expression and the production of IL-8 via reactive oxygen species and NF-kappaB activation. Moreover, CSM dramatically enhances the production of IL-8 in combination with TNF-alpha. Based upon the strong synergistic action, a combination therapy directed against ROS and TNF-alpha could be a new approach to stop the progression in lung damage during emphysema.

Cigarette smoke regulates the expression of TLR4 and IL-8 production by human macrophages.

BACKGROUND: Toll-like receptors (TLRs) are present on monocytes and alveolar macrophages that form the first line of defense against inhaled particles. The importance of those cells in the pathophysiology of chronic obstructive pulmonary disease (COPD) has well been documented. Cigarette smoke contains high concentration of oxidants which can stimulate immune cells to produce reactive oxygen species, cytokines and chemokines. METHODS: In this study, we evaluated the effects of cigarette smoke medium (CSM) on TLR4 expression and interleukin (IL)-8 production by human macrophages investigating the involvement of ROS. RESULTS AND DISCUSSION: TLR4 surface expression was downregulated on short term exposure (1 h) of CSM. The downregulation could be explained by internalization of the TLR4 and the upregulation by an increase in TLR4 mRNA. IL-8 mRNA and protein were also increased by CSM. CSM stimulation increased intracellular ROS-production and decreased glutathione (GSH) levels. The modulation of TLR4 mRNA and surface receptors expression, IRAK activation, IkappaB-alpha degradation, IL-8 mRNA and protein, GSH depletion and ROS production were all prevented by antioxidants such as N-acetyl-L-cysteine (NAC). CONCLUSION: TLR4 may be involved in the pathogenesis of lung emphysema and oxidative stress and seems to be a crucial contributor in lung inflammation.

Cells, mediators and Toll-like receptors in COPD.

Chronic obstructive pulmonary disease (COPD) is a global health problem. Being a progressive disease characterized by inflammation, it deteriorates pulmonary functioning. Research has focused on airway inflammation, oxidative stress, and remodelling of the airways. Macrophages, neutrophils and T cells are thought to be important key players. A number of new research topics received special attention in the last years. The combined use of inhaled corticosteroids and long-acting beta(2)-adrenoceptor agonists produces better control of symptoms and lung function than that of the use of either compound alone. Furthermore, collagen breakdown products might be involved in the recruitment and activation of inflammatory cells by which the process of airway remodelling becomes self-sustaining. Also, TLR (Toll-like receptor)-based signalling pathways seem to be involved in the pathogenesis of COPD. These new findings may lead to new therapeutic strategies to stop the process of inflammation and self-destruction in the airways of COPD patients.

Cigarette smoke stimulates the production of chemokines in mast cells.

Chronic obstructive pulmonary disease is a major health problem and will become the third largest cause of death in the world by 2020. It is currently believed that an exaggerated inflammatory response to inhaled irritants, in particular, cigarette smoke (CS), causes the progressive airflow limitation, in which macrophages and neutrophils are attracted by chemokines, leading to oxidative stress, emphysema, small airways fibrosis, and mucus hypersecretion. Smoking is also associated with an increase in mast cell numbers in bronchial mucosa. This study was conducted to determine the direct effects of CS on mast cell function, using murine bone marrow-derived mast cells (BMMC) as an in vitro model. BMMC were cultured from BALB/cBy mice for 3 weeks. Cells were treated with CS medium (CSM) for 30 min or 16 h. The effects of CSM on mast cell degranulation and chemokine production were measured. Moreover, we investigated the effect of CSM on IkappaB-alpha degradation and p38, Erk1/2, p65, and CREB expression by Western blotting. We found that CSM stimulated the release of chemokines in a noncytotoxic manner but did not induce mast cell degranulation. CSM induced phosphorylation of Erk1/2, p38, and CREB and increased translocation of p65 without degradation of IkappaB-alpha NF-kappaB in mast cells. The induction of chemokine production by CSM in mast cells could promote and prolong the inflammatory process. Our observations suggest that mast cells may contribute to the pathogenesis of emphysema through a direct effect of CS on the production of proinflammatory chemokines.

Combination of fluticasone propionate and salmeterol potentiates the suppression of cigarette smoke-induced IL-8 production by macrophages.

Cigarette smoke is the major risk factor for the development of chronic obstructive pulmonary disease (COPD). Macrophages are suggested to orchestrate the chronic inflammatory response and tissue destruction associated with COPD by secreting interleukin (IL)-8, a major neutrophil chemoattractant. The combination of inhaled corticosteroids and long-acting beta(2)-adrenoceptor agonists are increasingly used as maintenance therapy in patients with COPD. The aim of this study was to determine whether combined fluticasone propionate, a corticosteroid, and salmeterol, a long-acting beta(2)-adrenoceptor agonist, can suppress IL-8 production by human macrophages. To mimic resident macrophages in the lung, human monocytes were cultured for 5 days in medium containing Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF). In human Monocyte-Derived Macrophages, we found that cigarette smoke medium strongly enhanced IL-8 release in a time- and concentration-dependent manner. IL-8 release by cigarette smoke was significantly suppressed in a concentration-dependent manner by fluticasone and salmeterol. Coincubation of the drugs potentiated the inhibitory effect on cigarette smoke medium-induced IL-8 production and longer preincubation times resulted in more IL-8 inhibition. Interestingly, preincubation of cells with suboptimal concentration of salmeterol for 4 h before fluticasone administration for 30 min potentiates the inhibitory effect of fluticasone on IL-8 release. In conclusion, combination therapy may provide benefits over monotherapy for the treatment of COPD patients.

Toll-like receptor-4 mediates cigarette smoke-induced cytokine production by human macrophages.

BACKGROUND: The major risk factor for the development of COPD is cigarette smoking. Smoking causes activation of resident cells and the recruitment of inflammatory cells into the lungs, which leads to release of pro-inflammatory cytokines, chemotactic factors, oxygen radicals and proteases. In the present study evidence is found for a new cellular mechanism that refers to a link between smoking and inflammation in lungs. METHODS: Employing human monocyte-derived macrophages, different techniques including FACS analysis, Cytometric Bead Array Assay and ELISA were achieved to evaluate the effects of CS on pro-inflammatory cytokine secretion including IL-8. Then, Toll-like receptor neutralization was performed to study the involvement of Toll-like receptor-4 in IL-8 production. Finally, signaling pathways in macrophages after exposure to CS medium were investigated performing ELISA and Western analysis. RESULTS: We demonstrate that especially human monocytes are sensitive to produce IL-8 upon cigarette smoke stimulation compared to lymphocytes or neutrophils. Moreover, monocyte-derived macrophages produce high amounts of the cytokine. The IL-8 production is dependent on Toll-like receptor 4 stimulation and LPS is not involved. Further research resolved the cellular mechanism by which cigarette smoke induces cytokine production in monocyte-derived macrophages. Cigarette smoke causes subsequently a concentration-dependent phosphorylation of IRAK and degradation of TRAF6. Moreover, IkappaBalpha was phosphorylated which suggests involvement of NF-kappaB. In addition, NFkappaB-inhibitor blocked cigarette smoke-induced IL-8 production. CONCLUSION: These findings link cigarette smoke to inflammation and lead to new insights/therapeutic strategies in the pathogenesis of lung emphysema.