These data suggest that migratory DC differentiation in the peripheral tissues might be impaired if the activation

signals reach the monocyte precursors before their commitment to the DC differentiation pathway. Our data support this hypothesis by showing that activation of early MoDC precursors leads to inflammatory cytokine and chemokine production but the cells, at early stage of DC differentiation, have a limited ability to modulate their chemokine receptor expression required for lymph node homing. The cytokine producing ability of the developing inflammatory MoDCs can be terminated by the functional exhaustion before the cells differentiate to mature Decitabine research buy DCs capable of reprogramming their chemokine receptor profile. Early activation of developing MoDCs may thus set the threshold of DC migration to LNs, thereby limiting the continuous transfer of inflammatory signals to T lymphocytes.

Monocytes were isolated from buffy coats by Ficoll gradient centrifugation (Amersham Biosciences) and magnetic cell separation using anti-CD14–conjugated microbeads (Miltenyi Rapamycin mw Biotech). The purified cells were cultured at a density of 2×106 cells/mL in RPMI-1640 medium (Sigma-Aldrich, St. Louis, MO) supplemented with 10% FCS (Invitrogen), 75 ng/mL GM-CSF (Gentaur) and 100 ng/mL IL-4 (Peprotech EC). For DC activation we used the TLR ligands LPS, CL075, HKSA, Zymosan,

Pam3Cys or poly(I:C), all from Invivogen 3-mercaptopyruvate sulfurtransferase or soluble CD40L, INF-γ, TNF, IL-1 or IL-6 from Peprotech. Polyclonal IL-10 neutralizing antibodies and the goat isotype control Abs were purchased from R&D Systems. RNA was isolated from MoDCs precultured with or without 5 ng/mL LPS for 2 days using TRI reagent (Invitrogen) followed by a second purification on RNeasy coloumns coupled with DNase I treatement (Qiagen) according to the manufacturer’s recommendations. The extracted samples were labeled with Cy5, hybridized on Illumina Whole Genome HT12 microarrays, according to the manufacturer’s instructions. After scanning, bead-level data was converted into bead-summary data using the Illumina BeadStudio software. Prior to normalization, array probes were annotated using their sequence and converted to unique nucleotide identifiers (nuIDs). Background signal was assessed and corrected using the intensity signal from the control probes present on the array, and then quantile normalization was performed with the aid of the lumi R package 35. Microarray data has been submitted to the Array Express repository (accession number: E-MTAB-658). Differentially expressed genes were calculated using the Rank Product algorithm 36. differentially expressed genes were called significant when their corrected p-value (percentage of false positives) was equal to or lower than 0.05.

Together, these results identify Bcl11b as a central regulator of genes associated with T-cell maturation at the DP stage. The phenotype of the Lck-Cre-excised

mutants recapitulated that of mice with a germline disruption 25. These mice exhibited a severe differentiation block in DN cells, accompanied by a dramatic reduction in thymic cellularity, consistent with a role of Bcl11b in the survival of immature thymocytes 25. Importantly, loss of Bcl11b either in the germline (Bcl11bL−/L) or in the DN1-DN2 cells (Bcl11bL2/L2−Lckcre/+) preferentially affected the αβ T-cell lineage while appearing to spare γδ T cells. In both cases, a large percentage of Bcl11b-null cells expressed TCRγδ, most notably in the CD8+ population. TCRγδ expression might reflect impaired TCRβ rearrangement 25, and subsequent attempts by the BGB324 developing thymocyte to use a surrogate route of differentiation. Alternatively, Bcl11b may play a more active selleck chemicals llc role in the cell-fate choice between the αβ and the γδ lineages. This possibility

is supported by the strong upregulation of TCRγ transcripts in Bcl11b-deleted DP cells (>100× compared to WT, Supporting Information Table S1), suggesting a possible role of Bcl11b in repressing TCRγ expression. Note, however, that DP cells from Lck-Cre- (or CD4-Cre-) deleted mice did not exhibit surface TCRγδ expression (Supporting Information Fig. 7). As previously reported 26, disruption of the Bcl11b locus in DP cells resulted in a block in the differentiation into CD4+ and CD8+ SP cells. In addition, we observed a loss of canonical NKT cells in CD4-Cre-deleted mice, a T-cell population that has also been shown to differentiate from DP cells 43. However, the block in

T-cell differentiation in our mice appeared less severe than that reported by Albu et al. 26 – while we observed CD3hi (Fig. 2B) cell populations that were at least partially engaged into an SP differentiation process, such cells were apparently not as abundant in the mice described by these authors 26. These differences may possibly be attributed to differences in the timing of the deletion, as different CD4-Cre deleter lines were used in both studies, and/or genetic background differences. The large-scale changes in DNA ligase the gene expression program of DP cells appear to be at the heart of the mutant phenotype. In addition to the large number of genes encoding transcription factors that are dysregulated in DP cells from Bcl11bdp−/− mice (see above), Bcl11b also regulates expression of a variety of genes that play key roles in signaling cascades during T-cell differentiation (e.g. IL7R (up), Lck (down), Notch1 (up), and Jak1 (up)), and in ubiquitous pathways, such as ERK and PI3K/AKT (Supporting Information Fig. 5). Thus, Bcl11b appears to function as a master transcriptional regulator that is required for the harmonious interplay of numerous signaling cascades and transcriptional networks in DP thymocytes.

Because FoxP3 Alectinib ic50 expression is especially unstable in autoimmune states when strong antigenic stimulation is repeated [36,37], we suspect that the γ-PGA-induced aTreg cells that persist in the spleen may reconvert to non-Treg cells in the robust Th17-polarizing milieu of the CNS of EAE mice. Nevertheless, Treg instability, if any, did not diminish the therapeutic effect of γ-PGA on EAE, which may depend strongly on its suppression of Th17 responses. It should be noted that the finding that

γ-PGA suppresses Th17 cell development contradicts our previous report where it slightly induced Th17 cells [24]. This discrepancy may stem from differences between the Th17-polarizing conditions used in the two systems. We used more potent Th17-polarizing conditions containing anti-IFN-γ and anti-IL-4 neutralizing antibodies in the present study than in the previous one. We suspect that γ-PGA signals transduced in different contexts may elicit diverse effects. Most importantly, the in-vivo results obtained with the EAE model provide robust evidence that γ-PGA inhibits the differentiation of Th17 cells. In conclusion, we have shown that γ-PGA activates Selleck Ulixertinib two independent pathways in naive CD4+ T cells: a TLR-4/MyD88-dependent pathway that contributes to the induction

of Treg cells and a TLR-4/MyD88-independent pathway that inhibits the development of Th17 cells. In-vivo administration of γ-PGA ameliorated the symptoms of EAE. Thus, enough we have identified the MAMP γ-PGA as a novel regulator of autoimmunity, capable of rebalancing Th17/Treg

cells. Our findings highlight the potential of γ-PGA for treating diseases in which Th17 polarization plays a pathogenic role. We thank Drs Shizuo Akira and Myung-Shik Lee for providing MyD88-/- mice, Ms Eun-Hyun Kim for technical assistance and Dr Julian Gross for editorial assistance. This work was supported by a National Research Foundation grant funded by the Korean government (MEST; 2009-0081790). The authors state that they have no conflicts of interest. “
“The inflammatory cytokine IL-17 plays a critical role in immunity to infection and is involved in the inflammatory pathology associated with certain autoimmune diseases, such as psoriasis and rheumatoid arthritis. While CD4+ and CD8+ T cells are important sources of this cytokine, recent evidence has suggested that γδ T cells and a number of families of innate lymphoid cells (ILCs) can secrete IL-17 and related cytokines. The production of IL-17 by γδ T cells appears to be largely independent of T-cell receptor act-ivation and is promoted through cytokine signalling, in particular by IL-23 in combination with IL-1β or IL-18. Therefore IL-17-secreting γδ T cells can be categorised as a family of cells similar to innate-like lymphoid cells. IL-17-secreting γδ T cells function as a part of mucosal defence against infection, with most studies to date focusing on their response to bacterial pathogens.

The estimates of protection by BCG vaccination have ranged

from 0% to 80%.5 Hence, the development of more efficient vaccines capable of offering protection from TB disease is urgently needed. Cell-mediated immunity is known to be crucial for protection against TB disease.6,7M. tuberculosis resides primarily in the macrophage phagosome,8 Ivacaftor chemical structure a vacuolar compartment associated with MHC II antigen processing and presentation. MHC class II presentation of mycobacterial antigens by macrophages to CD4+ T cells is pivotal for a protective response against the disease.6,7,9–11 In addition, many studies have indicated that MHC class I restricted cytotoxic T lymphocytes (CTL) also play an important role in the control of M. tuberculosis infection.12,12–17 The identification of new CTL epitopes is therefore of importance for the analysis of the involvement of CD8+ T cells in GDC-0941 in vitro M. tuberculosis infections as well as for vaccine development. The identification of epitopes that have the potential of eliciting a CTL response has been greatly facilitated by the characterization of binding motifs for different MHC-I alleles of the 12 HLA-I supertypes.18 It is estimated

that nearly 100% of persons in all ethnic groups surveyed possessed at least one allele within at least one of the 12 supertypes. As a result, just 12 vaccine epitopes representing each of these 12 MHC-I supertypes would lead to almost complete population coverage. To date, however, only CTL epitopes restricted by a limited number of HLA molecules have been identified.19 Reverse immunology’ based on immuno-bioinformatics is maturing rapidly

and has now reached the stage where genome-, pathogen- and HLA-wide scanning for antigenic epitopes are possible at a scale and speed that makes it possible to exploit the genome information as fast as it can be generated. Immuno-informatic tools have been widely used for the in silico identification of T-cell epitopes from the proteomes of infectious micro-organisms including M. tuberculosis.20–25 We have previously used such approaches successfully C59 in vitro to identify T-cell epitopes derived from influenza A virus and vaccinia virus.26–28 In the present study, with the help of immuno-bioinformatics, M. tuberculosis-derived proteins were analysed in silico for CTL cell epitopes within the 12 HLA-I supertypes.18 The 9mer peptides corresponding to predicted epitopes were synthesized and affinity of binding to recombinant HLA class I molecules was measured. One hundred and fifty-seven 9mer peptides, predicted to bind to the 12 HLA class I supertypes, were shown to have high to intermediate binding affinity (KD < 500 nm) for the relevant HLA class I supertypes. These peptides were evaluated in vitro for their ability to stimulate T cells from strongly purified protein derivative (PPD) reactive donors to release interferon-γ (IFN-γ) in an ELISPOT assay.

Background: Haemodiafiltration (HDF) has recently been shown to have a mortality benefit over conventional HD thought possibly due to better clearance of middle-sized molecules

such as FGF-23 (32 kDa) and β2-microglobulin (13 kDa). These are known to be highly elevated in chronic HD patients and some, such as FGF-23, may be biomarkers for cardiovascular risk. However, it is unclear what convection volume is required to achieve sufficient removal to be associated with a mortality benefit. Methods: Stable satellite HD patients (thrice-weekly dialysis, n = 19) were selected from 3 satellite dialysis centres. At 2-week intervals, patients were changed from low-volume HDF (15L), to conventional high-flux HD, to high-volume HDF (25L). Biochemical samples were taken before and after the Autophagy pathway inhibitors mid-week treatment of the second week. Middle- (β2-microglobulin) and small-molecule removal were compared as reduction ratios for each compound. Paired t-tests were performed for statistical analysis.

Results: β2-microglobulin concentrations fell more with HDF than with conventional HD. The reduction ratios were as follows: HD 66.44%, HDF15L 76.48%, HDF25L 82.05% (P < 0.0001). No significant changes were observed in clearance of the following small molecules: potassium, phosphate and urea. Conclusions: Consistent Palbociclib with previous reports, HDF with higher convection volumes produces the greatest fall in β2-microglobulin concentrations. This and other middle molecule removal may contribute to the mortality benefits offered by HDF compared with conventional HD. 244 ADIPOSE TISSUE AND INFLAMMATION STATUS ON HEMODIALYSIS

PATIENTS IN BANDUNG INDONESIA R SUPRIYADI1, J JONNY1, R SOELAEMAN1, RMA ROESLI1, AH MARTAKUSUMAH1, RS GONDODIPUTRO1, R BANDIARA1, M RUDIANSYAH2, H PRIBADI, M ISMELIA1, D ASTRID L1 1Division of Nephrology & Hypertension, Department of Internal Medicine, Faculty of Medicine, L-NAME HCl Universitas Padjajaran/Hasan Sadikin Hospital Bandung; 2Division of Nephrology & Hypertension, Department of Internal Medicine, Faculty of Medicine, Universitas Lambung Mangkurat/Ulin Hospital Banjarmasin, Indonesia Aim: This study was conducted to describe the malnutrition and inflammation status on hemodialysis patients in Bandung, Indonesia. Background: Malnutrition and inflammation on hemodialysis (HD) patients are the most common conditions that could worsened and decrease the quality of life and increase morbidity and mortality of hemodialysis patients. Methods: Patients routinely on hemodialysis twice a week more than 3 months were recruited to the study.

PMMTM exposure reduced overall vasodilation in coronary arterioles compared with sham-treated animals; however, individual doses of Spermine NONOate were not significantly (p = 0.053 at 10 nm dose) different between exposure groups (max% 58 ± 7 sham, 46 ± 6 PMMTM, Figure 5A). Furthermore, endothelium-independent arteriolar dilation was different following PMMTM exposure in mesenteric arteries

beginning at the 10 nm (max% 70 ± 8 sham, 44 ± 8 PMMTM Figure 5A). Myogenic responsiveness of coronary arterioles was not different between sham and PMMTM-exposed FK228 concentration animals (Figure 5B). However, at 105 mmHg arterioles from PMMTM-exposed rats displayed a significantly greater myogenic learn more response to the highest transmural pressure (Figure 5B). This probably suggests an enhanced vascular smooth muscle cell contractile responsiveness to transmural pressure; however, the biological relevance of this effect is unclear at present. To determine the responsiveness of coronary and mesenteric arterioles to α-adrenergic stimulation, PE was performed. Neither coronary nor mesenteric arterioles showed any difference in reactivity to PE. Figure 6 depicts the maximal arteriolar constriction induced by PE in sham or PMMTM-exposed rats. This is the first study to demonstrate systemic microvascular effects of pulmonary exposure to particles

collected near active MTM sites. Furthermore, this study demonstrates that pulmonary PMMTM exposure results in acute microvascular dysfunction that (1) can be characterized across disparate vascular beds, (2) may be mediated through aberrant NO signaling, and (3) may also result from sympathetic nerve influences. The particle composition reported in Figure 1D is consistent with a predominantly crustal particle sample. MTM sites are active areas of blasting, crushing, and grinding of materials that can blanket the surrounding areas (-)-p-Bromotetramisole Oxalate with PM. In addition to mineralogical materials, engine exhaust emissions, likely off-road diesel, are

normally thought to contribute to the overall PM burden. Indeed, particle characterization from opencast mines suggests a mix of natural and exhaust emissions with the mass dominated by geological PM [23]. However, based on our results of a high OC measurement with null amounts of EC, the overall composition would suggest a particulate largely composed of mineralogical dust and coal dust [4]. Preliminary particle monitoring from these sites suggests that, by total number, ultrafine to 0.2 μm PM dominate the air sample (data not shown). This suggests that the bulk of the particles, by number, are anthropogenic in origin [46]. However, based on mass measurement (Figure 1D), the predominant particle composition is likely crustal.

For experiment in Fig. 1C, 5×104 presensitized MCs were mixed with equal amount of Tregs on microscope slides coated with 0.05 mg/mL poly-L-lysine, and incubated with DNP for 1 or 20 min at 37°C. Cells were fixed with 4% paraformaldehyde for 20 min, washed and mounted with Mowiol. Phase-contrast images were acquired and scoring of the slides was performed in a blinded fashion by evaluating for each condition at least 270 MCs in randomly selected fields from three independent experiments. Nearly, 2×105 presensitized BMMCs were loaded with 1 μM Fura2-AM (Molecular Probes), diluted in 0.5% Pluronic (Molecular

Probes) in DMSO, at room temperature for 10 min. Fura2-loaded BMMCs were plated together with equal number of Tregs onto poly-L-lysine-coated Idasanutlin in vivo coverslips and placed on the stage of an inverted fluorescence microscope (Olympus IX50, Olympus, Japan) equipped with a thermostated chamber (Harvard Apparatus, LY2109761 mouse MA, USA), at 37°C. To

analyze (Ca2+)i, a region was drawn around the BMMC and the fluorescence of Fura was used to determine the intracellular levels of free Ca2+ for total 25 min after Ag challenge. The changes in (Ca2+)i are expressed as a ratio of the light emitted at 505 nm upon excitation at the two wavelengths, 340 and 380 nm (F340/F380), after background subtraction. Data were collected using the TillVision Software (Till Photonics GmBH, Germany). Images were analyzed and processed using the ImageJ (Wayne Rasband, NIH; Bethesda, MD, USA) and with custom-made imaging software (Vimmaging, VIMM Padova).

To simultaneously check MC–Treg interactions over the acquisition time, interference contrast (DIC) images were kept at the beginning and at the end of each experiment. Branched chain aminotransferase Nearly, 4×106 presensitized BMMCs and 4×106 Tregs (ratio 1:1) were challenged with 100 ng/mL DNP-HSA (Sigma-Aldrich) in Tyrode’s buffer/0.05% BSA. After 10 min, cells were fixed by the addition of glutaraldehyde to reach 3% final concentration. Cells were kept for 3 h in 3% glutaraldehyde in 0.1 M phosphate buffer, pH 7.4, post-fixed in phosphate-buffered 1% osmium tetroxide for 1.5 h, dehydrated in graded ethanol series and embedded in Epon 812. Thin sections were counterstained with uranyl acetate and lead citrate and examined in a Philips CM 12 electron microscope at 80 kV. Nearly, 1×106 presensitized BMMCs and 1×106 Tregs (ratio 1:1) were challenged with 100 ng/mL DNP-HSA (Sigma-Aldrich) in Tyrode’s buffer/0.05% BSA for 30 min. LTC4 was measured by specific immunoassay (GE Healthcare) while the histamine concentration was determined by ELISA according to the producer’s instruction (DRG Instruments GmbH, Germany). β-Hexosaminidase was determined as previously described 4. For cytokine analysis, equal numbers of IgE-sensitized BMMCs and Tregs were cultured alone or together for 24 h in the presence of 100 ng/mL DNP.

, 2002), and studies using a B. burgdorferi CptA (carboxyl-terminal protease A) deletion mutant indicated that the C-terminal cleavage was likely a result of CptA proteolysis (Ostberg et al., 2004). P13 porin activity was detected using planar lipid bilayer assays, from which it was determined that P13 possesses cation-selective pores with a single channel conductance of 3.5 nS in 1 M KCl (Ostberg et al., 2002). This channel-forming activity was eliminated in a P13-deficient B. burgdorferi mutant (Ostberg et al., 2002). Unlike P66, however, P13 is not known to be associated GSI-IX nmr with virulence-related functions, and its expression has not been reported to be regulated by temperature or mammalian host-specific

signals. Interestingly, P13 is a member of a B. burgdorferi paralogous gene family, which contains eight additional plasmid-encoded P13 paralogs (Fraser et al., 1997; Noppa et al., 2001; Pinne et al., 2004). One of these paralogs, Selleckchem PLX3397 BBA01, displays channel-forming properties

similar to the chromosomally encoded P13 protein (Pinne et al., 2004, 2006). Furthermore, loss of the 3.5 nS membrane conductance from a p13 null mutant was restored by complementation with BBA01, suggesting that these proteins are possibly redundant at the functional level (Pinne et al., 2006). Although P13 and P66 have been verified to possess channel-forming activity characteristic of known bacterial porins, neither protein is structurally well characterized, and both P13 and P66 have been suggested to form atypical porin structures (Bunikis et al., 1995; Noppa et al., 2001; Pinne et al., 2004). P13 is predicted to span the OM by transmembrane α-helices, which is contrary to the amphipathic β-sheet-containing beta-barrel secondary structure typical of enteric Gram-negative proteobacterial porins (Koebnik et al., 2000; Schulz, 2002). Initially, P66 was also thought to span the membrane by two Selleckchem CHIR-99021 α-helical transmembrane domains (Bunikis

et al., 1995), although recent sequence analyses suggest that P66 may in fact form a 20-22-stranded β-barrel structure (Barcena-Uribarri et al., 2010). Future crystallography studies will be needed to fully delineate the P13 and P66 protein structures. Another B. burgdorferi protein termed Oms28, which is encoded by ORF bba74, was originally reported to be OM localized and to exhibit channel-forming activity (Skare et al., 1995, 1996). Additionally, Cluss and co-workers demonstrated that this protein was secreted from borrelial cells (Cluss et al., 2004). However, more recent biophysical and cellular localization data have suggested that BBA74 is a membrane-associated periplasmic protein that contains no integral membrane domains (Mulay et al., 2007). Surface-located membrane protein 1 (Lmp1), encoded by ORF bb0210, is a chromosomally encoded B. burgdorferi protein whose function, although still under investigation, may involve protection from host-adaptive immunity.

Radolf for providing B. burgdorferi strains and advice, Sam Behar and Steve Porcelli for providing antibodies to CD1, Nitin Damle and Vijay Sikand for performing the skin biopsies, and Jenny Shin for cutting sections of the EM biopsy samples. Conflict of interest: The authors declare no financial or commercial conflict of interest. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed,

but not copy-edited or typeset. They are made available as submitted by the authors. “
“Hepatitis is a common and potentially fatal manifestation of severe Coxsackievirus infections, particularly in newborn children. Little is known of the immune-mediated mechanisms regulating permissiveness GS-1101 to liver

infection. It is well established that type I interferons (IFNs) play an important role in the host innate immune response to Coxsackievirus infections. Recent learn more studies have highlighted a role for another IFN family, the type III IFNs (also called IFN-λ), in anti-viral defence. Whether type III IFNs are produced by hepatocytes during a Coxsackievirus infection remains unknown. Moreover, whether or not type III IFNs protects hepatocytes from a Coxsackievirus infection has not been addressed. In this study, we show that primary human hepatocytes respond to a Coxsackievirus B3 (CVB3) infection by up-regulating the expression of type III IFNs. We PD184352 (CI-1040) also demonstrate that type III IFNs induce an anti-viral state in hepatocytes characterized by the up-regulated expression of IFN-stimulated genes, including IFN-stimulated gene (ISG15), 2′-5′-oligoadenylate synthetase 2 (OAS2),

protein kinase regulated by dsRNA (PKR) and myxovirus resistance protein 1 (Mx1). Furthermore, our study reveals that type III IFNs attenuate CVB3 replication both in hepatocyte cell lines and primary human hepatocytes. Our studies suggest that human hepatocytes express type III IFNs in response to a Coxsackievirus infection and highlight a novel role for type III IFNs in regulating hepatocyte permissiveness to this clinically relevant type of virus. “
“Porphyromonas gingivalis, an anaerobic, asaccharolytic gram-negative bacterium, is a causative agent in chronic periodontitis. It has many virulence factors that facilitate infection of the gingiva, but little is known about the local immune cells that respond to this bacterium. The aims of this study were to quantify P. gingivalis in gingival biopsies from patients with periodontitis using laser capture microdissection (LCM) plus qRT-PCR and to determine the phenotype of immune cells associated with the bacteria using immunofluorescence. The presence of P. gingivalis was confirmed in periodontitis gingival tissue from 10 patients, and differences in bacterial distribution in the epithelium and connective tissue with or without inflammatory infiltrates were observed.

The concentration of C3a had a biphasic course in both groups, decreasing to preoperative values at T2 (30 min after surgery) only to rise again during the next 24 h. Median concentrations

of C3a at T3 were 185.9 ng/ml in group TIVA and 197.9 ng/ml in group INHALATION, respectively. A decrease in the levels of SC5b-9 compared to preoperative values was seen in both groups during surgery (P < 0.001). No significant differences regarding the levels of C3a and SC5b-9 were recorded between the treatment groups. The levels of the proinflammatory cytokines IL-6 and IL-8 increased during surgery and were elevated (P < 0.001) compared with baseline. No significant differences between the two groups were recorded for either cytokine. IL-6 reached a peak median concentration at T2 (30 min after surgery). The median concentration in group A-769662 cost TIVA was 1770 pg/ml, and in group INHALATION, the concentration was 1515 pg/ml. There were no significant differences between groups regarding concentrations of IL-6 at any time. The proinflammatory cytokine IL-8 followed a similar pattern over time. A peak concentration was measured at T2: median concentration in group TIVA was 99.6 pg/ml and in Roscovitine nmr group INHALATION was

96.8 pg/ml. No significant differences were recorded between the two groups. Regarding TNF-α and IL-1β, there was not an elevated concentration in any of the studied groups at any occasion. The concentration of the anti-inflammatory cytokine IL-10 was elevated in both groups. Peak concentrations were found in both groups after the operation was completed at T2: group TIVA 20.2 pg/ml and group INHALATION 67.4 pg/ml. There was a significant change in concentration of IL-10 compared with baseline in both groups (P < 0.001) over time, but no difference between the treatment groups. Regarding the concentration of IL-4, there was no significant difference in concentration over time or any difference between the

treatment groups. Linear mixed models did not identify any significant interactions between time and anaesthetic Orotidine 5′-phosphate decarboxylase type nor any significant pairwise comparisons at each time point after baseline. The analyses performed excluding patients with IBD (inflammatory bowel disease) again showed no significant differences between anaesthetic groups. This study shows that major colorectal surgery leads to activation of the complement cascade and the release of pro- and anti-inflammatory cytokines. Inflammatory activation is similar regardless of whether TIVA with propofol and remifentanil or inhalation anaesthesia with sevoflurane and fentanyl is used. A study by Ohmizo et al. [12] shows that propofol mixed with blood in vitro results in elevated levels of C3a. The levels were elevated to the same extent when blood was mixed with the lipid solvent of propofol, which suggests that it is the lipid solvent and not propofol itself that activates complement [12].