Long-term overexpression of human granulocyte colony-stimulating factor in transgenic mice: persistent neutrophilia with no increased mortality for more than one year

To investigate possible adverse consequences of persistent neutrophil overproduction, mice transgenic for human granulocyte colony-stimulating factor (hG-CSF) were studied for more than 1 year. They showed marked granulocytopoiesis and neutrophilia. Continuous medullary and extramedullary granulocytopoiesis resulted in marked changes in bone and liver. In the liver, haemorrhage and focal necrosis and a few haemangiosarcomas were present, presumably caused by the destructive granulocytopoiesis. Despite the high incidence of lung infiltration by mature neutrophils, lung lesions rarely appeared. Although there was a persistent increase in neutrophils, mortality of the mice did not differ from that of non-transgenic littermates at least within 1 year after birth. Factors other than overproduction of G-CSF and extensive neutrophilia could be required for the development of neutrophil-mediated acute and chronic tissue damage.     

Altered expression of endothelin, vascular endothelial growth factor, and its receptor in hepatic tissue in endotoxemic rat

Sepsis involves a heterogeneous class of syndromes, and septic shock, a severe form of sepsis, is associated with the development of progressive damage in multiple organs. The present study examined the time-dependent alterations of endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) levels in liver tissue in a septic rat model. Healthy male Wistar rats aged 15 weeks received 15 mg/kg lipopolysaccharide (LPS) and were sacrificed at different time points (1, 3, 6, and 10 hrs after treatment). Rats that did not receive LPS were considered to be controls. A 28-fold increase in the ET-1 level was observed in liver tissue 10 hrs after LPS administration. VEGF was also altered in hepatic tissue in a time-dependent manner. A gradual increase of VEGF expression in liver tissue after LPS administration was observed. Expression of Flt-1, the vascular permeability receptor of VEGF, was also increased in liver tissue after LPS administration. ET-1 is a potent vasoconstrictor and, therefore, may play a role in the regulation of hepatic perfusion in a sepsis model. On the other hand, VEGF may be involved in capillary leakage in liver tissue after LPS administration. The present findings suggest that there might be a loss of balance between the ET-1 and VEGF levels in the septic liver at different time points, which could contribute to the pathogenesis of acute liver injury in endotoxemia.     

3H]thymidine incorporation into whole liver as an alternative to [3H]thymidine incorporation into DNA as a parameter of cell proliferation in regenerating liver tissue in rats

OBJECTIVE: To monitor liver regeneration following partial hepatectomy, liver cell proliferation can be measured by assaying in vivo [3H]thymidine incorporation into liver cell DNA. We hypothesized that [3H]thymidine incorporation into whole liver tissue parallels [3H]thymidine incorporation into liver cell DNA, both in high proliferating and low proliferating liver. STUDY DESIGN: Liver cell proliferation in rats after partial hepatectomy or a sham operation was studied by measuring incorporation of [3H]thymidine into various fractions of liver tissue on days 1, 2, 3, 4 and 10 after surgery. RESULTS: [3H]thymidine incorporation into whole liver tissue and in the protein fraction correlated well with DNA-specific [3H]thymidine incorporation into regenerating (r > .80, P < .0001) and nonregenerating liver (r > .69, P < .005). [3H]thymidine incorporation into DNA was < 5% of the total amount of administered [3H]thymidine in both sham-operated and hepatectomized rats. Significant differences in [3H]thymidine incorporation into partially hepatectomized livers as compared to sham-operated rat livers were found on days 1 and 2 (whole liver tissue and protein fraction) or day 1 (DNA) after surgery. CONCLUSION: [3H]thymidine incorporation into whole liver tissue is a simple technique that can be used for the study of liver cell proliferation after partial hepatectomy in rats.     

犬传染性肝炎DNA疫苗安全性评价

目的研究犬传染性肝炎核酸疫苗pVAX1-CpG-Loop的安全性。方法 BALB/c小鼠随机分为4组,高剂量组(肌内注射每只200μg)、低剂量组(肌内注射每只100μg)、联合免疫组(肌内注射每只100μg,皮下注射50μg,滴鼻每只50μg)和PBS组,每两周免疫1次,共免疫3次。末次免疫后4周、6个月检测血常规和血液生化及对F1代的影响,用PCR和RT-PCR的方法检测DNA疫苗的生物学分布和存留时间,末次免疫后4周和6个月取脏器观察病理损伤。结果各剂量组的主要血液学检测指标、对F1代的影响差异无显著性。末次免疫后4周各剂量组AST明显高于对照组。DNA疫苗在注射部位可存留8周,其中高剂量组和低剂量组在肝、脾、肾和注射部位有分布,联合免疫组在肺组织也有分布。末次免疫后4周小鼠肝肾有淋巴细胞浸润,6个月后慢性炎症明显好转。结论由犬传染性肝炎病毒DNA疫苗引起的肝肾损伤是一过性的,并且pVAX1-CpG-Loop没有整合到宿主基因组,也没有传递给F1代。     

Systematic investigation of degradation effects on spin-spin relaxation times in mouse-liver by low resolution NMR

Despite numerous work on spin-lattice (T1) relaxation in vitro, not much attention has been paid on spin-spin (T2) relaxation until now. In this study we are presenting spin-spin relaxation time measurements of mouse liver tissue in order to estimate the time-after-excision effects. The post mortem behaviour of excised tissue was investigated up to four hours in intervals of about nine minutes. The time course of liver T2 was determined for different temperatures (4 degrees - 40 degrees C) for female mice. In order to describe the similar behaviour of T2 and pH changes in mouse liver after excision, we are suggesting an empirical model to correlate this data. In contrast to T1 results published recently, we found no significant differences in liver T2 time course after excision due to different physiological states like sex, starvation or circadian rhythm. T1/T2-behaviour after tissue excision is discussed in an attempt to separate various relaxation mechanisms.     

脐带间充质干细胞移植对慢性试验性肝损伤的治疗作用

目的观察脐带间充质干细胞（UC-MSC）对慢性实验性肝损伤的治疗作用并探讨其分子生物学机理。方法 50只7周龄的NOD/SCID小鼠注射四氯化碳（CCL4）制备慢性肝损伤模型后,应用随机数字表的方法随机将实验小鼠随机分成2组：模型组（25只）和UC-MSC移植组（25只）。UC-MSC移植组通过尾静脉注射移植1×106 UC-MSC,模型组注射同样体积的PBS。分别于移植后1、2、3和4周收集肝组织,应用免疫组织化学,RT-PCR和Western blot的方法分析细胞移植前后肝组织的病理生理学特征的变化。采用t检验和方差分析进行统计学分析。结果 UC-MSC移植治疗后肝组织表达人肝细胞特异性AFP,Alb,和内皮细胞特异性CD31,Flk-1。细胞移植4周后v WF标记的血管密度明显增加,同时伴有部分的肝功能改善,谷丙转氨酶（ALT）水平从（55.71±11.33）U/L减至（36.75±12.80）U/L（P〈0.05）。此外,本研究结果表明UC-MSC分泌几种重要的生长因子HGF,FGF-2,VEGF,和VEGF受体通过旁分泌的途径发挥肝组织修复的功能。结论在CCL4诱导的慢性肝损伤模型肝组织,人UC-MSC可以分化成肝细胞样细胞和内皮细胞样细胞,同时旁分泌多种细胞生长因子修复损伤的肝细胞,并伴有肝功能的改善。认为UCMSC移植或许成为将来肝脏损伤疾病一个重要的治疗选择。     

Changes of insulin binding in rat tissues after exposure to stress.

The effects of various stressors on insulin receptors in adipose, liver and skeletal muscle tissues were studied in rats exposed to acute or repeated stress. Adult male rats were exposed to immobilization (IMO) for 2.5 hours daily for 1, 7 and 42 days, or to hypokinesia (HK) for 1, 7 and 21 days. We determined the values of specific insulin binding (SIB) and insulin receptor binding capacity (IR) of plasma cell membranes from adipose, liver and muscle tissue (IMO groups), or insulin binding to isolated adipocytes and hepatocytes (HK groups). A significant decrease of SIB and IR was observed in rats exposed to acute stress (1x IMO) in muscle, adipose and liver tissues. However, in animals exposed to repeated stress (7x and 42x IMO), SIB and IR were diminished in the muscle tissue, whereas no significant changes were noted in the liver and adipose tissue. When tissue samples were collected 3-24 hours after exposure to IMO stress, no changes of SIB and IR were found in liver and adipose tissue, but insulin binding was lowered in skeletal muscles. In animals exposed to HK for one day, a decrease of SIB and IR was found in isolated adipocytes, but no changes in insulin binding were noted in the liver tissue. In rats exposed to HK for 7 and 21 days, values of IR were similar as in control group. Our results indicate a) the different changes of IR in the liver, fat and muscle tissues after exposure to stress situations, b) a long-term decrease of insulin binding in muscles of rats exposed to repeated IMO stress, and c) the return of reduced SIB and IR (induced by acute stress) to control values in the liver and adipose tissue after a short recovery period.     

‘Are fish what they eat’ all year round?

Isotope turnover in muscle of ectotherms depends primarily on growth rather than on metabolic replacement. Ectotherms, such as fish, have a discontinuous pattern of growth over the year, so the isotopic signature of muscle (δ¹³C and δ¹⁵N) may only reflect food consumed during periods of growth. In contrast, the liver is a regulatory tissue, with a continuous protein turnover. Therefore, the isotopic composition of liver should respond year round to changes in the isotopic signature of food sources. Therefore, we predicted that (1) Whitefish in Lake Geneva would have larger seasonal variation in the isotopic variation of the liver compared to that of the muscle tissue, and (2) the isotope composition of fish muscle would reflect a long-term image of the isotope composition of the food consumed only throughout the growth period. To test these expectations, we compared the isotope compositions of Whitefish muscle, liver and food in a 20-month study. We found that the seasonal amplitude of isotope variation was two to three times higher in liver compared to muscle tissue. During the autumn and winter, when growth was limited, only the isotopic signature of liver responded to changes in the isotope composition of the food sources. The δ¹³C and δ¹⁵N of muscle tissue only reflected the food consumed during the spring and summer growth period.     

Evaluation of YO-PRO-1 as an early marker of apoptosis following radiofrequency ablation of colon cancer liver metastases

Radiofrequency (RF) ablation (RFA) is a minimally invasive treatment for colorectal-cancer liver metastases (CLM) in selected nonsurgical patients. Unlike surgical resection, RFA is not followed by routine pathological examination of the target tumor and the surrounding liver tissue. The aim of this study was the evaluation of apoptotic events after RFA. Specifically, we evaluated YO-PRO-1 (YP1), a green fluorescent DNA marker for cells with compromised plasma membrane, as a potential, early marker of cell death. YP1 was applied on liver tissue adherent on the RF electrode used for CLM ablation, as well as on biopsy samples from the center and the margin of the ablation zone as depicted by dynamic CT immediately after RFA. Normal pig and mouse liver tissues were used for comparison. The same samples were also immunostained for fragmented DNA (TUNEL assay) and for active mitochondria (anti-OxPhos antibody). YP1 was also used simultaneously with propidium iodine (PI) to stain mouse liver and samples from ablated CLM. Following RFA of human CLM, more than 90 % of cells were positive for YP1. In nonablated, dissected pig and mouse liver however, we found similar YP1 signals (93.1 % and 65 %, respectively). In samples of intact mouse liver parenchyma, there was a significantly smaller proportion of YP1 positive cells (22.7 %). YP1 and PI staining was similar for ablated CLM. However in dissected normal mouse liver there was initial YP1 positivity and complete absence of the PI signal and only later there was PI signal. Conclusion: This is the first time that YP1 was applied in liver parenchymal tissue (rather than cell culture). The results suggest that YP1 is a very sensitive marker of early cellular events reflecting an early and widespread plasma membrane injury that allows YP1 penetration into the cells.     

Systematic investigation of degradation effects on spin-lattice relaxation times in mouse-liver by low resolution NMR

In spite of numerous work on in vitro proton relaxation time investigations of biological tissue, many questions still remain open. In this study we focused on spin-lattice (T1) relaxation time measurements of mouse liver tissue in order to estimate the time-after-excision effects. The post mortem behaviour of excised tissue was measured up to four hours in intervals of about nine minutes. The time course of liver T1 was determined for different temperatures (4 degrees-40 degrees C) for female mice and the effect of starvation (up to 48 hours) on the time course of T1 was investigated for male and female mice at 37 degrees C. We obtained significant differences in liver T1 time course after excision due to different physiological states like sex, starvation and circadian rhythm.     

The human glutathione S-transferases: Developmental aspects of the GST1, GST2, and GST3 loci

The expression of the GST1, GST2, and GST3 loci in fetal, neonatal, and infant tissues has been studied using starch gel electrophoresis and chromatofocusing. Each locus demonstrated developmental changes in expression, some of which were specific to a single tissue while others occurred in several tissues. GST1 was not usually expressed in any of the tissues studied before 30 weeks of gestation but steadily increased thereafter until adult levels were reached in late infancy. In neonates and older infants the frequencies of the GST1*0, GST1*1, and GST1*2 alleles were 0.79, 0.07, and 0.14, respectively. GST2 was always expressed in liver and adrenal but was only weakly expressed in spleen, cardiac muscle, and diaphragm. In kidney this locus was not usually expressed until nearly 1 year after birth. The GST3 isoenzymes were present in all fetal, neonatal, and infant tissues, although their expression in liver decreased after 30 weeks of gestation. Other isoenzymes with fast anodal mobilities were also identified in several tissues; these are believed to be GST3 isoenzymes that have undergone posttranslational modification rather than products of the putative GST4 locus. No specifically fetal isoenzymes were detected.     

Alteration of apoptotic protease-activating factor-1 (APAF-1)-dependent apoptotic pathway during development of rat brain and liver.

Brain and liver extracts of rats at different stages after birth were examined for cytochrome c/dATP-dependent caspase (DEVDase)-activation (mitochondria pathway) in vitro. The caspase-activating activity in the brain extracts rapidly decreased after birth, reaching approximately 50 and 5%, at 1 and 2 weeks, respectively, of that in a 3-days- newborn sample, and essentially no caspase-activation was detected in the adult rat brain extracts. Such a dramatic change was not detected in the liver samples, suggesting that the observed abrogation of the cytochrome c-dependent mitochondria pathway after birth is a brain-specific event. In order to determine the factor(s) lacking in adult brain, we separately measured Apaf-1, procaspase 9, and pro-DEVDase activities using a supplementation assay. In adult brain, Apaf-1 activity was scarcely detected, while the tissue retained low but significant amounts of procaspase 9 (16% of that in the fetal tissue) and a pro-DEVDase (3.4%). In contrast, adult liver extracts retained relatively high levels of all of these factors. Immunoblot analyses clearly indicated that the expression of Apaf-1 and procaspase 3 is markedly suppressed within 4 weeks after birth in brain tissue while they are even expressed in adult liver. Considering these results together, we propose that, in the brain, the cytochrome c-dependent mitochondria pathway, which is essential for the programmed cell death during normal morphogenesis, is abrogated within 2-4 weeks after birth, whereas the pathway is still active in other adult tissues such as liver.     

Partial structure and hormonal regulation of rabbit liver inhibitor-1; distribution of inhibitor-1 and inhibitor-2 in rabbit and rat tissues

Inhibitor-1 purified from rabbit liver could not be distinguished from the skeletal muscle protein by chromatographic, electrophoretic and immunological criteria. Amino acid sequences comprising 68% of rabbit liver inhibitor-1 were identical to the skeletal muscle protein indicating that they are products of a single gene. Total inhibitor-1 activity in heat-treated rabbit liver extracts was similar to that in skeletal muscle extracts, and the phosphorylation state of inhibitor-1 increased from 14% to 42% in rabbit liver in vivo after an intravenous injection of glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-1 recognised a single major protein of identical electrophoretic mobility (26 kDa) in each rabbit tissue examined (skeletal muscle, liver, brain, heart, kidney, uterus and adipose). The antibodies also recognised a single major (30 kDa) protein in the same rat tissues, except liver. The results show that while there are interspecies differences in apparent molecular mass, inhibitor-1 is likely to be the same gene product in each mammalian tissue. Inhibitor-1 was not detected in rat liver, either by activity measurements or immunoblotting, irrespective of the age, sex or strain of the animals. Immunoblotting also failed to detect inhibitor-1 in mouse liver, although it was present in guinea pig, porcine and sheep liver. The absence of inhibitor-1 in rat liver indicates that phosphorylation of this protein cannot underlie the increased phosphorylation of hydroxymethylglutaryl-CoA reductase observed after stimulation by glucagon. Monospecific antibodies to rabbit skeletal muscle inhibitor-2 recognised a 31 kDa protein in each rabbit tissue, and a 33 kDa protein in all rat tissues including liver. The results suggest that inhibitor-2 is the same gene product in each mammalian tissue.     

VEGFR1-Positive Macrophages Facilitate Liver Repair and Sinusoidal Reconstruction after Hepatic Ischemia/Reperfusion Injury

Liver repair after acute liver injury is characterized by hepatocyte proliferation, removal of necrotic tissue, and restoration of hepatocellular and hepatic microvascular architecture. Macrophage recruitment is essential for liver tissue repair and recovery from injury; however, the underlying mechanisms are unclear. Signaling through vascular endothelial growth factor receptor 1 (VEGFR1) is suggested to play a role in macrophage migration and angiogenesis. The aim of the present study was to examine the role of VEGFR1 in liver repair and sinusoidal reconstruction after hepatic ischemia/reperfusion (I/R). VEGFR1 tyrosine kinase knockout mice (VEGFR1 TK^-/- mice) and wild-type (WT) mice were subjected to hepatic warm I/R, and the processes of liver repair and sinusoidal reconstruction were examined. Compared with WT mice, VEGFR1 TK^-/- mice exhibited delayed liver repair after hepatic I/R. VEGFR1-expressing macrophages recruited to the injured liver showed reduced expression of epidermal growth factor (EGF). VEGFR1 TK^-/- mice also showed evidence of sustained sinusoidal functional and structural damage, and reduced expression of pro-angiogenic factors. Treatment of VEGFR1 TK^-/- mice with EGF attenuated hepatoceullar and sinusoidal injury during hepatic I/R. VEGFR1 TK^-/- bone marrow (BM) chimeric mice showed impaired liver repair and sinusoidal reconstruction, and reduced recruitment of VEGFR1-expressing macrophages to the injured liver. VEGFR1-macrophages recruited to the liver during hepatic I/R contribute to liver repair and sinusoidal reconstruction. VEGFR1 activation is a potential therapeutic strategy for promoting liver repair and sinusoidal restoration after acute liver injury.     

Early growth response (EGR)-1 is required for timely cell-cycle entry and progression in hepatocytes after acute carbon tetrachloride exposure in mice

Cell-cycle induction in hepatocytes protects from prolonged tissue damage after toxic liver injury. Early growth response (Egr)-1(-/-) mice exhibit increased liver injury after carbon tetrachloride (CCl(4)) exposure and reduced TNF-α production. Because TNF-α is required for prompt cell-cycle induction after liver injury, here, we tested the hypothesis that Egr-1 is required for timely hepatocyte entry into the cell cycle after CCl(4)-induced liver injury. Acute liver injury was induced by a single injection of CCl(4). Assays were employed to assess indices of the cell cycle in liver after CCl(4) exposure. Bromodeoxyuridine incorporation peaked in wild-type mice at 48 h after CCl(4) but was reduced by 80% in Egr-1(-/-) mice. Proliferating-cell nuclear-antigen immunohistochemistry revealed blocks in cell-cycle entry and progression to DNA synthesis in Egr-1-deficient mice 48 h after CCl(4). Cyclin D, important for G0/G1 progression, was reduced at baseline and 36 h after CCl(4). Cyclin E1, required for G1/S-phase transition, was reduced in Egr-1(-/-) mice 24 and 48 h after CCl(4) exposure and was associated with reduced phosphorylation of the retinoblastoma protein. Proliferation in Egr-1(-/-) mice was delayed, rather than blocked, because indices of cell-cycle progression were restored 72 h after CCl(4) exposure. We concluded that Egr-1 was required for prompt cell-cycle entry (G0- to G1-phase) and G1/S-phase transition after toxic liver injury. These data support the hypothesis that Egr-1 provides hepatoprotection in the CCl(4)-injured liver, attributable, in part, to timely cell-cycle induction and progression.     

Changes in activities of some ammonia-metabolizing enzymes in the rat liver and the brain after chronic ethanol administration

The changes in the activities of ammonia-metabolizing enzymes in liver and brain after ethanol intoxication has been investigated in rats. After administration of ethanol 30% (w/v) 6g kg-1 for 4 weeks we found an increase in liver glutamate dehydrogenase and glutaminase activity. In brain tissue the glutaminase activity was significantly higher and glutamate dehydrogenase was significantly lower. Glutamine synthetase activity in liver and brain was practically unchanged. The reasons for these changes in the activities of some ammonia-metabolizing enzymes in liver and brain after ethanol ingestion have been discussed.     

酒精性肝病合并HBV感染并发肝衰竭对NF-κB信号通路的影响

由于酗酒人数的增长,HBV感染合并酒精性肝病患者的数量在中国逐年增加,酒精性肝病与HBV感染会严重影响肝功能。目前中国已成为引起肝硬化的第二大病因。而乙型肝炎病毒感染合并酒精性肝病是最常见的,且会对肝脏造成严重的损伤。本实验的检测了NF-κB信号通路和IL-8、TNF-α和Cleaved caspase-3基因及蛋白的表达,结果表明,酒精性肝病合并HBV感染并发肝衰竭会激活NF-κB信号通路,并上调IL-8、TNF-α和Cleaved caspase-3基因和蛋白的表达,说明酒精性肝病合并HBV感染不仅对肝脏造成了极其严重的损伤,还造成肝脏组织或细胞炎症的发生和细胞凋亡及组织纤维化。通过以上的研究,本实验为揭示酒精性肝病合并HBV并发肝衰竭的分子机制,以及为后续研究酒精性肝病合并HBV并发肝衰竭的靶向治疗提供理论参考。     

强力霉素在斑点叉尾(鲴)体内药物动力学及残留消除规律研究

研究利用高效液相色谱法研究了强力霉素在斑点叉尾 (Ictalurus punctatus)体内的药物动力学与消除规律, 有助于制定合理用药方案和休药期, 为水产品质量安全提供理论依据。(1)单次口服剂量 20 mg/kg 强力霉素在斑点叉尾 体内的药时数据符合二室开放式模型。药-时曲线呈明显双峰现象: 第一次达峰时, 强力霉素在肾、血和肌肉中浓度迅速上升, 达峰时间 Tmax (1)出现在 30min, 强力霉素在肝脏中浓度上升缓慢, 出现在 1h; 肝、肾、血和肌肉第二次达峰的时间 Tmax (2)出现在 8h, 第二次达峰浓度 Cmax(2)大于第一次的浓度Cmax (1)。 药-时曲线下面积(AUC): 肾、肝、血和肌肉分别为 63.242、1282.077、142.379、62.348 μg·h /mL。消除半衰期[T1/2b]: 肾、肝、血和肌肉分别为 40.668、48.767、36.527、31.091h, 平均滞留时间(MRT): 肾、肝、血和肌肉分别为 46.585、56.989、48.859、42.428h; (2)连续口服剂量 20 mg/kg 的强力霉素 5d, 停药后强力霉素在斑点叉尾 肝脏中浓度最高, 肌肉+皮中浓度最低。在不同组织中强力霉素的消除速率不同(P<0.05), 药物消除速度由高到低依次为肌肉+皮、肾脏、肝脏。若以肝脏为靶组织, 最高残留限量 300 μg/kg,休药期不低于 30d; 若以可食组织肌肉+皮为靶组织, 最高残留限量 300 μg/kg, 休药期不低于 19d。     

Prolonged survival of transplanted islets of Langerhans encapsulated in a biocompatible membrane

Prolonged survival of islet allografts in streptozotocin-induced diabetic rats was achieved by encapsulating individual islets in protective, biocompatible alginate-polylysine-alginate membranes. A single intraperitoneal transplant of encapsulated islets reversed the diabetic state for up to 1 year. In contrast, a single injection of unencapsulated islets was effective for less than 2 weeks. The microencapsulation procedure, by protecting transplanted tissue from the components of the immune system, has great clinical potential in the treatment of diseases requiring organ transplantation, such as diabetes and liver disease.     

Adipose and liver expression of interleukin (IL)-1 family members in morbid obesity and effects of weight loss

Morbid obesity is associated with a state of chronic inflammation. Interleukin-1 family (IL-1F) cytokine members are produced by human adipose tissue in obesity. Whereas certain IL-1F members such as IL-1β or IL-18 are potently proinflammatory, others such as IL-1 receptor antagonist (IL-1Ra) or IL-37 (formerly IL-1F7) are antiinflammatory. The NLRP3 inflammasome plays a key role in the processing of bioactive IL-1β and IL-18. We investigated the effect of excessive weight loss on subcutaneous adipose tissue and liver expression of IL-1α, IL-1β, IL-18, IL-1Ra, IL-37 and NLRP3. Twenty-one severely obese patients undergoing laparoscopic adjustable gastric banding were studied. Tissue samples were collected before and 6 months after laparoscopic adjustable gastric banding surgery. mRNA expression of all studied IL-1F members, but especially of IL-37, was much higher in subcutaneous/visceral adipose tissue compared with their liver expression. Subcutaneous adipose tissue mRNA expression of IL-1β decreased significantly after extensive weight loss; expression of IL-18 and IL-1Ra did not change, whereas IL-37 expression increased. Weight loss led to a significant reduction in liver IL-1β, IL-18 and IL-1Ra expression, whereas hepatic IL-37 mRNA expression remained stable. Adipose/liver NLRP3 inflammasome and IL-1α expression were not affected by weight loss. Tissue expression of IL-1β, IL-18 and IL-37 were significantly higher in subcutaneous/visceral adipose tissue compared with the liver. In conclusion, expression of IL-1F members is more pronounced in adipose compared with liver tissue in patients with severe obesity. Excessive weight loss changes the adipose and liver expression profile of IL-1F members toward a more antiinflammatory direction.