Hepcidin is a key regulator of iron metabolism and a mediator of anemia in inflammation. Recent in vitro studies recognized prohepcidin as a type II acute phase protein regulating via interleukin-6. The aim of the present study was to investigate the time course of plasma prohepcidin after a large cardiac surgery in relation to IL-6 and other inflam matory parameters. Patients with chronic thromboembolic hypertension (n=22, males/females 14/8, age 51.9±10.2 years) underwent pulmonary endarterectomy using cardiopulmonary bypass and deep hypothermic circulatory arrest were included into study. Arterial concentrations of prohepcidin, IL-1β , IL-6, IL-8, tumor necrosis factor-α , and C-reactive protein were measured before/after sternotomy, after circulatory arrest, after separation from bypass, and then 12, 18, 24, 36, 48 h and 72 h after the separation from bypass. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. Pulmonary endarterectomy induced a 48 % fall in plasma prohepcidin; minimal concentrations were detected after separation from cardiopulmonary bypass. Prohepcidin decline correlated with an extracorporeal circulation time (p<0.01), while elevated IL-6 levels were inversely associated with duration of prohepcidin decline. Postoperative prohepcidin did not correlate with markers of iron metabolism or hemoglobin concentrations within a 72-h period after separation from CPB. Prohepcidin showed itself as a negative acute phase reactant during systemic inflammatory response syndrome associated with a cardiac surgery. Results indicate that the evolution of prohepcidin in postoperative period implies the antagonism of stimulatory effect of IL-6 and contraregulatory factors inhibiting prohepcidin synthesis or increasing prohepcidin clearance., P. Maruna ... [et al.]., and Obsahuje seznam literatury
We investigated the differences between the lavage parameters - including tumour necrosis factor-a (TNF-a) and interferon-y (IFN-y) release by lavage leukocytes - in control rats and in animals intratracheally instilled with short and long amosite and wollastonite fibres. These cytokines can play an important role in lung disease development after long-term exposure to some fibrous dusts. Short and long amosite and wollastonite fibres were intratracheally instilled in rats (1 mg/week) for ten weeks while saline was given to controls. To compare the harmful effects of these fibres, the number of leukocytes/ml of bronchoalveolar lavage (BAL), the number of alveolar macrophages (AM) per ml of BAL, AM:granulocyte (GR) ratios in lavage fluid, phagocytic activity and viability of AM, lactate dehydrogenase (LDH), acid phosphatase (AcP), and TNF-a and IFN-y release by lavage leukocytes were investigated 3 months after the first intratracheal instillation. Compared with the controls, amosite short fibres significantly decreased the numbers of AM/ml BAL, and increased their phagocytic activity and AcP release. Long amosite fibres significantly decreased the numbers of AM/ml BAL, increased the number of granulocytes depressed the phagocytic activity and viability of AM, and significantly decreased the levels of TNF-a and IFN-y in supernatants of cultured leukocytes. While wollastonite short and long fibre instillation did not significantly influence the parameters studied (except for a significantly increased number of leukocytes/ml BAL in wollastonite long fibres), amosite short and long fibres caused marked differences in these parameters, the long fibres being more effective.
The liver fluke Clonorchis sinensis (Digenea) is a high-risk parasite that causes serious diseases such as cirrhosis, carcinogenic liver damage and clonorchiasis in East Asia. This study was conducted to evaluate the relationship between stress/endocrine hormones and inflammation induced by infection as well as the expression of heat shock proteins (hsp-27, hsp-90), cox-2 and cytokines in the livers of hamsters infected with C. sinensis. The average body weight of infected hamsters decreased up to 25% compared with that of the control group, and bile duct hyperplasia with inflammation, liver fibrosis and hepatic necrosis were observed in C. sinensis-infected livers. The expression of hsp-27, hsp-90, and cox-2 was significantly increased in the livers of C. sinensis-infected hamsters compared with the control group. Moreover, the expression levels of inflammatory cytokines (IL-1β, IL-2, TGF-β2 and IFN-α1) were markedly increased in the livers of the infected group compared with those of the control group. Consistently, plasma IL-3 and IL-6 levels gradually increased during the infection period, and the concentration levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), corticosterone, and adrenocorticotropic hormone (ACTH) in C. sinensis-infected hamsters increased over 25%, compared with those of the uninfected normal group. These results demonstrate that C. sinensis infection may increase the expression of hsp27, hsp90 and cox-2 as well as it may cause periductal fibrosis, chronic inflammation and hepatic necrosis in the liver. Furthermore, the results indicate that C. sinensis infection induces not only stress-induced hormone imbalance but also the sustained secretion of inflammatory cytokines through chronic stress/stimuli.
To evaluate whether the response of hematopoietic cells to interleukin-17 (IL-17) depends on the tissue microenvironment in which hematopoiesis occurs, the influence of recombinant mouse IL-17 on spleen hematopoietic cells and cytokine release was assessed in normal mice in vitro and in vivo. In vitro, IL-17 did not significantly affect the growth of granulocyte-macrophage (CFU-GM) and erythroid (BFU-E and CFU-E) derived colonies. A single injection of IL-17 in vivo exhibited stimulatory effects on hematopoietic cells from both granulocytic and erythroid lineages. The increased number of metamyelocytes 48 h after treatment imply to the IL-17-induced stimulation of granulopoiesis. The number of BFU-E was increased at 24 h, while the number of CFU-E increased 6 h and 24 h after treatment. Since the same treatment in the bone marrow decreased the number of CFU-E, it may be concluded that the local microenvironment plays an important role in IL-17-mediated effects on CFU-E. IL-17 increased the release of IL-6 both in vitro and in vivo, but showed tendency to suppress the constitutive secretion of IL-10 by spleen cells. Our results suggest the complexity of target cell response and interplay of secondary induced cytokines by IL-17 in different hematopoietic organs., G. Jovčić, D. Bugarski, A. Krstić, M. Vlaški, M. Petakov, S. Mojsilović, N. Stojanović, P. Milenković., and Obsahuje bibliografii a bibliografické odkazy
Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver-related morbidity and mortality. The aim of this work was to establish and characterize a nutr itional model of NAFLD in rats. Wistar or Sprague-Dawley male rats were fed ad libitum a standard diet (ST-1, 10 % kcal fat), a medium-fat gelled diet (MFGD, 35 % kcal fat) and a high-fat gelled diet (HFGD, 71 % kcal fat) for 3 or 6 weeks. We examined the serum biochemistry, the hepatic malondialdehyde, reduced glut athione (GSH) and cytokine concentration, the respiration of liver mitochondria, the expression of uncoupling protein-2 (UCP-2) mRNA in the liver and histopathological samples. Feeding with MFGD and HFGD in Wistar rats or HFGD in Sprague-Dawley rats induced small-droplet or mixed steatosis without focal infl ammation or necrosis. Compared to the standard diet, there were no significant differences in serum biochemical parameters, except lower concentrations of triacylglycerols in HFGD and MFGD groups. Liver GSH was decreased in rats fed HFGD for 3 weeks in comparison with ST-1. Higher hepatic malondialdehyde was found in both strains of rats fed HFGD for 6 weeks and in Sprague-Dawley groups using MFGD or HFGD for 3 weeks vs. the standard diet. Expression of UCP-2 mRNA was increased in Wistar rats fed MFGD and HFGD for 6 weeks and in Sprague-Dawley rats using HFGD for 6 weeks compared to ST-1. The present stud y showed that male Wistar and Sprague-Dawley rats fed by HFGD developed comparable simple steatosis without signs of progression to non-alcoholic steatohepatitis under our experimental conditions., O. Kučera ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Cytokines are widely known mediators of inflammation accompanying many neurodegenerative disorders including normal pressure hydrocephalus (NPH). NPH is caused by impaired cerebrospinal fluid (CSF) reabsorption and treated by surgical shunt insertion. The diagnostics is still complicated and the shunt effect is not durable; after several years, dementia may develop. In the clinical practice, biomarkers support the diagnostics as well as the further time course of many neurodegenerative diseases. Until recently, no reliable biomarker for NPH was evaluated. The attempt of this review was to make a survey concerning cytokines as possible NPH markers. Among all reviewed cytokines, the most promising are CSF IL-10 and IL-33, enabling to follow-up the disease progression and monitoring the effectiveness of the shunt insertion., L. Sosvorova, M. Mohapl, J. Vcelak, M. Hill, J. Vitku, R. Hampl., and Obsahuje bibliografii
This comparative study of various surface treatments of commercially available implant materials is intended as guidance for orientation among particular surface treatment methods in term of the cell reaction of normal human osteoblasts and blood coagulation. The influence of physicochemical surface parameters such as roughness, surface free energy and wettability on the response of human osteoblasts in the immediate vicinity of implants and on the blood co agulation was studied. The osteoblast proliferation was monitored and the expression of tissue mediators (TNF-α , IL-8, MMP-1, bone alkaline phosphatase, VCAM-1, TGF-β ) was evaluated after the cell cultivation onto a wide range of commercially available materials (titanium and Ti6Al4V alloy with various surface treatments, CrCoMo alloy, zirconium oxide ceramics, polyethylene and carbon/carbon composite). The formation of a blood clot was investigated on the samples immersed in a freshly drawn whole rabbit blood using scanning electron microscope. The surfaces with an increased osteoblast proliferation exhibited particularly higher surface roughness (here Ra > 3.5 μm) followed by a high polar part of the surface free energy whereas the effect of wettability played a minor role. The surface roughness was also the main factor regulating the blood coagulation. The blood clot formation analys is showed a rapid coag ulum formation on the rough titanium-based surfaces. The titanium with an etching treatment was considered as th e most suitable candidate for healing into the bone tissue due to high osteoblast proliferation, the highest production of osteogenesis markers and low production of inflammatory cytokines and due to the most intensive blood clot formation., D. Kubies ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Mangiferin is a kind of polyphenol chemical compound separated from these herbal medicines of Mangifera indica L., Anemarrhena asphodeloides Bge. and Belamcanda chinensis L., which has anti-inflammatory, anti-virus, and other physiological activities without toxic effects. Osteoarthritis (OA) is a chronic disease that is also a kind of arthritis disease in which articular cartilage or bones under the joint is damaged. In addition, artificial replacements are required in severe cases. At present, there are not too much researches on the potential biological activities of mangiferin that plays a protective role in the treatment of OA. In this study, we evaluated the protective effect of mangiferin on osteoarthritis (OA) in vitro and in vivo. First, the effect of different concentrations of mangiferin on rat chondrocytes was determined by MTT assay. Second, the effects of mangiferin on the expression levels of matrix metalloproteinase (MMP)-13, TNF-α, Collagen II, Caspase-3, and cystatin-C in interleukin-1β (IL-1β)-induced rat chondrocytes were examined by the real-time polymerase chain reaction in vitro, meanwhile the effects of mangiferin on the nuclear factor kappa-B (NF-κB) signaling pathway were also investigated by Western Blot. Finally, the antiosteoarthritic protective effect of mangiferin was evaluated in the rat model by anterior cruciate ligament transection (ACLT) combined with bilateral ovariectomy-induced OA in vivo. The results showed that the mangiferin was found to inhibit the expression of MMP-13, TNF-α, and Caspase-3 which also increased the expression of Collagen II and cystatin-C in IL-1β-induced rat chondrocytes. In addition, IL-1β-induced activation of nuclear factor kappa-B (NF-κB) and the degradation of inhibitor of κB (IκB)-α were suppressed by mangiferin. For the in vivo study in a rat model of OA, 100 μl of mangiferin was administered by intra-articular injections for rats, the results showed that the cartilage degradation was suppressed by mangiferin through Micro CT and Histological Examination. According to both in vitro and in vivo results, mangiferin has a protective effect in the treatment of OA which may be a promising therapeutic agent for OA.
Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve a nd inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They br ought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-α and other proinflammatory cytokines prod uction and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey's inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of va gally-mediated anti-inflammatory pathway in the treatment strategies., I. Zila, D. Mokra, J. Kopincova, M. Kolomaznik, M. Javorka, A. Calkovska., and Obsahuje bibliografii
Starling’s original definition of a hormone from 1905 was “a hormone is a substance produced by glands with internal secretion, which serve to carry signals through the blood to target organs”. Today, this definition is understood to be lacking, but newer definitions also do not encompass the entire meaning of hormones as specific carriers of information. One main problem is that there is no delineation between hormones and other signaling molecules such as cytokines, growth factors or autacoid compounds. It seems that a precise definition is not even possible, since some cytokines and growth factors, such as the cytokines erythropoietin, lipocalin-2 and asprosin or fibroblast growth factor 23, act as hormones under certain conditions., Luboslav Stárka, Michaela Dušková., and Obsahuje bibliografii