1C). To verify the functional impact of the induction of mitochondrial genes we measured COX and citrate synthase (a nuclear-encoded mitochondrial matrix marker of citrate cycle) enzyme activity in total liver lysates. As expected, the analyses confirmed that the specific activities of the two enzymes were increased in LivPGC1-β hepatocytes as compared with the www.selleckchem.com/products/CAL-101.html controls (Fig. 1D). In summary, liver-specific PGC1-β

overexpression is able to induce mitochondrial functions through the induction of proteins involved in citrate cycle and oxidative phosphorylation, as well as to enhance the expression of genes involved in TG biosynthesis. To test whether the ability of PGC1-β overexpression to increase the expression of genes encoding for proteins involved in TG biosynthesis could cause changes in the circulating lipids, we measured serum lipid levels of wildtype and LivPGC1-β mice fed a standard diet (chow diet). Different from previous data reporting that overexpression of PGC1-β by way of adenovirus infections

dramatically increases TG levels in the blood,20 we only recorded a slight, but significant, induction in serum TG levels of LivPGC-1β mice http://www.selleckchem.com/products/MK-2206.html when compared with their littermate controls (Fig. 2A). However, after the injection of Triton WR-1339 that prevents the catabolism of VLDL by inhibiting lipoprotein lipase activity, the level of TG secretion of LivPGC-1β mice fed with a normal chow diet was 3-fold higher than control littermates (Fig. 2B). Given that PGC-1β is also able to induce the expression of genes involved in fatty acid catabolism and since the serum TG levels did not reach 2-fold induction in LivPGC-1β mice despite their higher TG secretion rate, we decided to test whether PGC-1β could induce an efficient substrate switch in response to a lipid overload. For this purpose, we administered an intragastric olive oil load by gavage to wildtype and LivPGC-1β mice and followed the clearance of serum TG and NEFAs at different timepoints. Strikingly, whereas both wildtype and LivPGC-1β mice showed a massive increase

learn more in TG levels at 2 hours after administration of olive oil in LivPGC-1β mice the TG concentration returned to almost normal levels 4 hours after the fat load. In contrast, in wildtype mice TG concentrations reached basal levels only 6 hours from oil injection, suggesting that overexpression of PGC-1β in the liver promotes TG clearance from the blood under the condition of lipid overload (Fig. 2C). A similar effect was observed for the serum concentration of NEFAs, although their clearance was blunted if compared with TG clearance (Fig. 2D). Taken together, these data imply that specific overexpression of PGC-1β in the liver leads to TG and NEFA clearance by activating mitochondrial β-oxidation of fatty acids.

1C). To verify the functional impact of the induction of mitochondrial genes we measured COX and citrate synthase (a nuclear-encoded mitochondrial matrix marker of citrate cycle) enzyme activity in total liver lysates. As expected, the analyses confirmed that the specific activities of the two enzymes were increased in LivPGC1-β hepatocytes as compared with the http://www.selleckchem.com/products/Vorinostat-saha.html controls (Fig. 1D). In summary, liver-specific PGC1-β

overexpression is able to induce mitochondrial functions through the induction of proteins involved in citrate cycle and oxidative phosphorylation, as well as to enhance the expression of genes involved in TG biosynthesis. To test whether the ability of PGC1-β overexpression to increase the expression of genes encoding for proteins involved in TG biosynthesis could cause changes in the circulating lipids, we measured serum lipid levels of wildtype and LivPGC1-β mice fed a standard diet (chow diet). Different from previous data reporting that overexpression of PGC1-β by way of adenovirus infections

dramatically increases TG levels in the blood,20 we only recorded a slight, but significant, induction in serum TG levels of LivPGC-1β mice FK506 cell line when compared with their littermate controls (Fig. 2A). However, after the injection of Triton WR-1339 that prevents the catabolism of VLDL by inhibiting lipoprotein lipase activity, the level of TG secretion of LivPGC-1β mice fed with a normal chow diet was 3-fold higher than control littermates (Fig. 2B). Given that PGC-1β is also able to induce the expression of genes involved in fatty acid catabolism and since the serum TG levels did not reach 2-fold induction in LivPGC-1β mice despite their higher TG secretion rate, we decided to test whether PGC-1β could induce an efficient substrate switch in response to a lipid overload. For this purpose, we administered an intragastric olive oil load by gavage to wildtype and LivPGC-1β mice and followed the clearance of serum TG and NEFAs at different timepoints. Strikingly, whereas both wildtype and LivPGC-1β mice showed a massive increase

click here in TG levels at 2 hours after administration of olive oil in LivPGC-1β mice the TG concentration returned to almost normal levels 4 hours after the fat load. In contrast, in wildtype mice TG concentrations reached basal levels only 6 hours from oil injection, suggesting that overexpression of PGC-1β in the liver promotes TG clearance from the blood under the condition of lipid overload (Fig. 2C). A similar effect was observed for the serum concentration of NEFAs, although their clearance was blunted if compared with TG clearance (Fig. 2D). Taken together, these data imply that specific overexpression of PGC-1β in the liver leads to TG and NEFA clearance by activating mitochondrial β-oxidation of fatty acids.

We then discuss its relative importance in comparison with alternative mechanisms that could be maintaining genetic and phenotypic diversity. The idea that the fitness of an organism is affected by the relative frequencies of the genotypes in

a population was first described by Fisher (1930), suggesting that an inverse relation between the two could maintain stable polymorphisms. This concept was later formalized by other researchers, such as Li (1955), Wright (1956) and Lewontin (1958), who developed mathematical models to describe the mechanism. Evidence that the fitness of a morph depends on its frequency relative to the frequencies of the other morphs was first found by Wright & Dobzhansky (1946) in an experimental Anti-infection Compound Library population of Drosophila pseudoobscura. this website Three different gene arrangements can be found in the third chromosome of this species, and their frequencies were observed to fluctuate over the year in natural populations. Wright and Dobzhansky set up an experimental population with known frequencies of the different genotypes and controlled environmental conditions. They found that the observed changes in frequencies of the phenotypes at different temperatures fitted the predictions of a model where the fitness of the homozygotes decreases

as their frequencies increase, while the fitness of the heterozygotes remains constant. However, Wright and Dobzhansky considered this hypothesis to be an ‘extreme’ one. Since then, there have been several laboratory studies where evidence for NFDS has been found in populations of Drosophila, with morph frequencies fluctuating selleckchem in a manner that is predictable based on the known effects of frequency on

fitness (Levene, Pavlovsky & Dobzhansky, 1954; Kojima & Tobari, 1969; Anderson & Brown, 1984; Singh & Chatterjee, 1989). A correlation between fitness and frequency has also been found in laboratory studies in crustaceans (Maskell et al., 1977; Duncan & Little, 2007), land snails (Tucker, 1991) and water snails (Koskella & Lively, 2009). This correlation has been found in natural populations as well, and is the commonest form of evidence supporting NFDS in the wild (Reid, 1987; Gross, 1991; Seehausen & Schluter, 2004; Svensson et al., 2005; Olendorf et al., 2006; Bleay et al., 2007; Takahashi & Watanabe, 2010). A few studies have also demonstrated oscillations in morph frequencies over time that can be explained by NFDS (Hori, 1993; Sinervo & Lively, 1996). However, direct evidence for NFDS in the wild is generally scarce because the best way to test for it is to manipulate the frequencies of different morphs in a population, and to obtain reliable measures of fitness from individuals of each morph, both of which pose considerable practical challenges.

Estimates were based on caregiving from family members only, and did not include costs associated with caregiving from nonfamily members (e.g., friends, neighbors). Moreover, cost estimates were based only on assistance with ADLs and IADLs and did not include other time-consuming caregiving activities such as transportation to a hospital for clinic visits, laboratory tests, paracenteses, or variceal banding. Similarly, our cost estimates do not include other significant caregiving costs such as out-of-pocket expenses related to medications, medical

supplies, or lost wages (patient or caregiver) related to cirrhosis. A recent study by Bajaj et al. highlighted these other cirrhosis-related expenses and the detrimental effect they can have on patients’ ability to adhere to medical recommendations.4 This population-based study confirms the significant burden PD-1 antibody and cost that cirrhosis and its complications places upon the patient and caregiver, as well as the health care system. Clinicians should be aware of the increased need for informal caregiving among patients with cirrhosis, especially older individuals with other age-related comorbidities. In addition, health care economists and policy makers should consider the significant functional limitations of this population as AZD1152-HQPA price well as the substantial hours of informal caregiving required to help avert preventable poor

outcomes related to the patients’ inability to independently manage their disease. Greater focus on a comprehensive delivery of care for patients with cirrhosis, including involvement of caregivers and improved care coordination, is necessary to optimize management of this frail population. “
“Background and Aim:  Serrated adenomas (SAs), recently subdivided into traditional SAs (TSAs) and sessile SAs (SSAs),

are recognized as a distinct form of neoplasia of the colorectum. One of the characteristics of SAs is hypermaturation of the gland epithelium due to the low extent of cell loss by apoptosis. Mutations of mitochondrial DNA this website (mtDNA) are closely associated with abnormality in apoptosis. We therefore examined mtDNA mutations in colorectal lesions including hyperplastic polyps (HPs), SSAs, TSAs, and carcinomas. Methods:  Examined were 25 HPs, 32 SSAs, 19 TSAs, and 138 carcinomas. The D310 region of the mtDNAs was examined by microsatellite assay. Results:  mtDNA mutations were detected in none of 25 (0%) HPs, one of 32 (3%) SSAs, six of 19 (32%) TSAs, and eleven of 133 (8%) carcinomas (five of the 138 carcinomas were not informative). The frequency of mtDNA mutations in the TSAs was significantly higher than that in the HPs, SSAs, and carcinomas (P = 0.004, P = 0.008, and P = 0.009, respectively). The frequency of mtDNA mutations in carcinomas was not significantly higher than that in HPs and SSAs (P = 0.14 and P = 0.28, respectively).

Figures 2 and 3 describe the associations

between IL-1B −31 CC plus TT (homozygous group), as compared with IL-1B −31 CT, and between IL-1B −31 CC plus CT (C carrier group), as compared with IL-1B −31 TT, and gastric carcinoma risk; Figure 4 presents IL-1B +3954 TT plus CT (T carrier group), compared with +3954 CC; and Figure 5 presents IL-1B RN *2/*2 plus *2/L (*2 selleck compound carrier group), compared with RN L/L, distinctly. For overall gastric carcinoma, statistically significant findings could be found in such associations when the pooled OR (95%CI, P-value) associated with IL-1B −511 T carriers versus CC genotypes were 1.23 (1.04–1.45, P = 0.015) and with RN *2 carriers versus L/L 1.26 (1.06–1.51, P = 0.010), respectively; but no statistically significant findings could be found in such associations when the pooled OR (95%CI, P-value) associated see more with −31 CC plus TT versus CT, −31 C carriers versus TT, and +3954 T carriers versus CC were 0.92 (0.82–1.03, P = 0.147), 0.97 (0.84–1.11, P = 0.651), and 1.23 (0.92–1.65, P = 0.171), respectively. As shown in Tables 1–5,

specific data were stratified, on the basis of sample size, into two subgroups: large sample (the numbers of both controls and cases not less than 200) and small and moderate-sized sample subgroups (the numbers of controls and cases less than 200). As for large sample subgroups, statistically significant findings could be found in such associations when the pooled OR (95%CI, P-value) for −31 CC plus TT versus CT and for IL-1RN 2 carriers versus LL were 0.85 (0.76–0.96, P = 0.008) and 1.28 (1.05–1.57, P = 0.016), respectively. As for small and moderate-sized sample subgroups, statistically significant findings could be found only when the pooled OR (95%CI, P-value) for −511 T carriers versus CC was 1.25 (1.07–1.46, P = 0.005). The data were also stratified, in accordance with the

quality selleck appraisal scores, into high-quality (scores no less than 7) and low- and moderate-quality (scores less than 7) subgroups. Except for statistically significant findings found only when the pooled OR (95%CI, P-value) in IL-1RN *2 carriers versus L/L was 1.34 (1.03–1.74, P = 0.029) for the low- and moderate-quality subgroup, no statistically significant findings could be found in the other high-quality or low- and moderate-quality subgroups. The data were additionally stratified, in line with publication time, into the subgroup of articles published after 2006 and the counterpart of articles published prior to or in 2006. Statistically significant findings were found on the grounds that the pooled OR (95%CI, P-value) for −511 T carriers versus CC in the subgroup of articles published prior to or in 2006 and IL-1B RN *2/L versus L/L in the subgroup of articles published after 2006 were 1.22 (1.01–1.48, P = 0.035) and 1.51 (1.20–1.89, P = 0.000), respectively.

MMP-12 was exclusively colocalized to F4/80-positive cells, confirming macrophages as a source of MMP-12. To confirm MMP-12 expression in F4/80-positive cells, we isolated hepatic macrophages from a short model of CCl4 injury. Following isolation of hepatic macrophages, the purity of F4/80-enriched and F4/80-depleted populations was assessed by qPCR (Fig. 4D). Quantitation of MMP-12 mRNA showed that the macrophage-enriched cell population had higher expression of MMP-12 than the macrophage-depleted

population (Fig. 4D). Overall, this demonstrates that MMP-12 in www.selleckchem.com/products/ink128.html different species is expressed by a population of hepatic macrophages in the fibrotic liver and mechanistically linked to elastin degradation. In

order to define mechanistically the role of MMP-12 and elastin degradation in the development of fibrosis, we exposed MMP-12−/− mice and C57Bl/6 WT controls to either CCl4 or olive oil for 12 weeks. Animals were sacrificed 48 hours after the last injection. Serum markers of hepatocyte damage (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) in the knockout were comparable to those of the WT (Supporting data). Picrosirius red staining PCI-32765 order and collagen I immunohistochemistry indicated that CCl4 induced an identical degree of fibrosis in the WT and MMP-12−/− animals (Fig. 5A,B, respectively). Quantification of either staining by image analysis did not show a significant difference between the groups (data not shown). Despite the fact that no difference in overall fibrosis could be detected, immunohistochemistry for elastin did show a subtle phenotypic difference between the WT and MMP-12 null mice. Figure 5C shows high-power representative images of elastin immunohistochemistry in the WT and the knockout after CCl4 administration. On close examination the MMP-12−/− mice showed clear evidence

of perisinusoidal elastin that was not detected in the WT controls. The quantification by percentage of positive find more fields containing elastin in Fig. 5D shows that there was a significant increase of perisinusoidal elastin in the MMP-12−/− fibrotic livers (P = 0.004). Because elastin is a late feature of fibrosis, we hypothesized that the relatively short duration of the injury highlighted a subtle phenotype only. We determined that a model of protracted low-level injury was necessary to more robustly highlight the role of MMP-12 in elastin turnover. Thus, MMP-12−/− mice and C57Bl/6 WT controls were given dietary TAA (600 mg/L in drinking water) for 52 weeks. Figure 6A shows representative images of elastin immunostaining in the WT and the knockout mice in undamaged liver and after TAA administration. Quantification by image analysis showed that TAA significantly increased elastin deposition in the knockout (P = 0.015), but not in the WT (Fig. 6A5).

This may be because biopsy sampling is relatively benign, subsequent mortality or injury is unknown, or it may also be due to underreporting by researchers, who are unlikely to publish accounts of these events. The one exception is a published description of the death

of a common dolphin (Delphinus delphis) following biopsy sampling (Bearzi 2000). In this report, the author claimed that the death was not a direct consequence of the biopsy wound, but rather, the result of a combination of several variables, including the malfunction of the stopper on the dart, the location on the body where the biopsy dart was embedded in the animal, click here the thinness of the individual’s blubber layer relative to other animals in the population, handling of the animal by the sampling team after the biopsy event, and possibly a predisposition of this individual dolphin to catatonia and death during stressful events (Bearzi 2000). Although mechanical and

human error played a role in this tragic event, Bearzi (2000) stated that identical methods had been used on other common dolphins with no, or only minor and temporary, behavioral responses. Thus, the author had considered the technique to be relatively noninvasive. This report demonstrates that individuals within the same species can exhibit variable responses to darting, and if assessment of body condition in the field is possible, biopsy EX527 sampling animals in poor condition should be avoided. The author also concluded that research methods should only be adopted after careful review and risk assessment and that those decisions must be reviewed on a regular basis (Bearzi 2000). For example, the Tethys Research Institute website lists pros and cons of biopsy sampling and outlines the organization’s guidelines and policies on biopsy sampling, including

the recent policy to cease biopsy darting small cetaceans (http://www.tethys.org/internal/biopsy.htm, accessed 27 September 2010). In addition to monitoring biopsy wounds, systematic assessments of behavioral responses to biopsy sampling are important. Researchers have occasionally monitored cetaceans during and after biopsy darting to assess the impact of the sampling selleckchem equipment and protocols on behavior. Unlike monitoring the healing process of wounds, assessing behavioral responses is more subjective. A number of researchers have used video cameras to record behavioral reactions during biopsy sampling attempts (Barrett-Lennard et al. 1996, Berrow et al. 2002, C. Emmons3), and some of these cameras were attached to the firing device to enable simultaneous collection of a tissue sample and a video record of the biopsy site. This technique allows researchers to identify sampled animals, assess immediate wounds, and more accurately quantify an animal’s reaction to sampling events.

Additional details are provided in the Supporting Information. HEK293T, Chinese hamster ovary, Buffalo rat liver, Huh7, Huh7.5-GFP, and Huh7.5.1 cells were cultured as described.18, 23-25 Primary human hepatocytes were isolated as described.18 Chinese hamster ovary and Buffalo rat liver cells expressing SR-BI were produced as described.11, 15, 23 Polyclonal15 and monoclonal antibodies (mAbs) directed against the extracellular loop of SR-BI were raised by genetic immunization of Wistar rats and

Balb/c mice as described15 according to proprietary technology (Aldevron GmbH, Freiburg, Germany). Anti–SR-BI mAbs were purified using protein G affinity columns and selected via flow cytometry for their ability to bind to human SR-BI.15 To determine the affinity of the anti–SR-BI mAbs for human SR-BI, Huh7.5.1 cells were incubated

with increasing concentrations of mAbs, and binding was assessed using Alisertib molecular weight flow selleckchem cytometry. Kd values were determined as half-saturating concentrations of the mAbs.26, 27 Antibodies will be provided on request using a material transfer agreement (MTA). Anti-CD81 (JS-81), anti–SR-BI (CLA-1), and phycoerythrin-conjugated anti-mouse antibodies were from BD Biosciences. Anti-His and fluorescein isothiocyanate–conjugated anti-His antibodies were obtained from Qiagen, rabbit anti-actin (AA20-30) antibodies were obtained from Sigma-Aldrich, and mouse anti-NS5A antibodies were obtained from Virostat. Anti-E1 (IGH520, IGH526, Innogenetics), anti-E2 (IGH461, Innogenetics; AP33, Genentech; CBH23, a kind gift from S.K.H. Foung), and patient-derived

anti-HCV immunoglobulin G (IgG) have been described.16, see more 25, 27 Luciferase reporter cell culture-derived HCV (HCVcc), HCV pseudoparticles (HCVpp), murine leukemia virus pseudoparticles, and vesicular stomatitis virus glycoprotein pseudoparticles (VSV-Gpp), infection and kinetic experiments have been described.15, 18, 25, 27, 28 Unless otherwise stated, HCVcc experiments were performed using Luc-Jc1, and infection was analyzed in cell lysates via quantification of luciferase activity.29 For combination experiments, each antibody was tested individually or in combination with a second antibody. Huh7.5.1 cells were preincubated with anti–SR-BI or control mAb for 1 hour and then incubated for 4 hours at 37°C with HCVcc (Luc-Jc1) or HCVpp (P02VJ) (preincubated for 1 hour with or without anti-envelope antibodies). Synergy was assessed using the combination index and the method of Prichard and Shipman.30-32 Cell viability was assessed using a MTT test.2 Recombinant His-tagged soluble E2 (sE2) was produced as described.23 Huh7.5.1 cells were preincubated with control or anti–SR-BI serum (1:50), anti–SR-BI or control mAbs (20 μg/mL) for 1 hour at room temperature, and then incubated with sE2 for 1 hour at room temperature. Binding of sE2 was revealed using flow cytometry as described.18, 23 Huh7.5.

FMD was assessed as the

percentage change from baseline to maximal diameter of the brachial VX-809 chemical structure artery with reactive hyperemia. The average of three measurements at each timepoint was used to derive the maximum FMD. Repeated measurements on the same subjects (that were done in 50 controls randomly selected from the 150 healthy study children) gave coefficients of variation less than 10%. For the American Heart Association (AHA),14 MS is diagnosed in the presence of any three of the following five constituent risks: central obesity as determined by WC, hypertension, low HDL values, elevated triglyceride values, and glucose impairment. We used the pediatric AHA definition,15 which is based on the AHA adult definition but uses pediatric reference standards for BP, WC, triglycerides, and HDL cholesterol. Thus, in our study central obesity was defined as a WC ≥90th percentile for age and gender; hypertriglyceridemia as triglycerides ≥90th percentile for age and gender; low HDL cholesterol as concentrations ≤10th percentile for age and gender; elevated BP as systolic or diastolic BP ≥90th percentile for age, gender, and height percentile;

and impaired fasting glucose as glucose ≥5.6 mmol/L. IR was determined by a homeostasis model assessment of insulin resistance (HOMA-IR).16 We considered HOMA-IR values ≥90th percentile for age and sex of those observed in our population of healthy lean subjects as an indicator of IR. Statistical analyses were performed using the SPSS package. Data are expressed selleck products either as frequencies or means learn more with 95% confidence intervals (CIs).

Distributions of continuous variables were examined for skewness and kurtosis and were logarithmically transformed, when appropriate. Geometric means are reported for total and HDL cholesterol, triglycerides, APO A-1, APO B, CRPHS, insulin, and HOMA-IR values. Differences between groups were tested for significance using analysis of variance (ANOVA) for quantitative variables with the Bonferroni correction for multiple comparisons, and chi-square test for qualitative variables. Pearson’s correlation and linear regression coefficients were used to examine the relationship between variables, both in the entire population and separately in controls and in obese children. The independence of the association of NAFLD with FMD as well as with cIMT was assessed by multivariate linear regression analysis (when the dependent variable was continuous) or logistic (when the dependent variable was dichotomous). For this purpose, subjects were stratified into those having FMD ≤10th percentile of values observed in healthy lean subjects versus those showing FMD >10th. Likewise, increased cIMT was defined as ≥90th percentile of values observed in healthy lean subjects.

7). The genetic deletion of Ostα leads first to alterations in bile acid homeostasis, increasing formation of Fgf15 and inhibition of Cyp7a1, resulting in a smaller bile acid pool size in these animals.1, 2 When these animals are subjected to BDL, the endocrine actions of Fgf15 are eliminated because bile acids GSK-3 activity are now excluded from

the intestine, resulting in up-regulation of bile acid synthesis and hepatic basolateral membrane bile acid export transporters. Finally, the inability of the kidney to reabsorb bile acids because of the absence of Ostα, in association with further down-regulation of Asbt and up-regulation of renal Mrp2 and Mrp4, all result in a significant escape route for bile acids in the urine that does not normally occur to this

extent in the conventional adaptive response of the kidney to cholestasis. This finding has significant therapeutic implications because strategies to down-regulate Ostα in the kidney should have major clinical benefits Ibrutinib clinical trial in cholestatic liver injury by further augmenting the renal excretion of bile acids and thus diminishing their hepatic and systemic accumulation, as shown in this study. We thank Kathy Harry for technical assistance and Christine L. Hammond for help with the collection and analysis of hepatic bile. Additional Supporting Information may be found in the online version of this article. “
“Transient hepatomegaly often accompanies acute bacterial infections. Reversible, dose-dependent hepatomegaly also occurs when animals are given intravenous infusions of bacterial lipopolysaccharide (LPS). We found that recovery from LPS-induced hepatomegaly requires a host enzyme, acyloxyacyl hydrolase (AOAH), that inactivates LPS. When we challenged Aoah−/− mice with low doses of LPS or Gram-negative bacteria, their livers remained enlarged (as much as 80% above normal) many weeks longer than did the livers of Aoah+/+

animals. When compared with livers from LPS-primed Aoah+/+ mice, LPS-primed Aoah−/− livers had (1) more numerous and larger Kupffer cells, (2) intrasinusoidal leukocyte aggregates and activated sinusoidal endothelial cells, and (3) sustained production selleck compound of interleukin (IL)-10 and messenger RNAs (mRNAs) for tumor necrosis factor (TNF), IL-10, and IRAK-M. Depleting Kupffer cells decreased the liver enlargement by ≈40%, whereas depletion of neutrophils, dendritic cells, natural killer (NK) cells, NK-T cells, or B cells had no effect. Pretreatment with dexamethasone almost completely prevented prolonged hepatomegaly in Aoah−/− mice, whereas neutralizing TNF or interleukin-1β was only partially effective. In contrast, an antagonistic antibody to the IL-10 receptor increased LPS-induced hepatomegaly by as much as 50%. Conclusion: our findings suggest that persistently active LPS induces Kupffer cells to elaborate mediators that promote the accumulation of leukocytes within enlarged sinusoids.