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Background Bloodstream infection and sepsis are major causes of health loss worldwide, and it is important to identify patients at risk of developing and dying from these conditions. The single-nucleotide polymorphism most strongly associated with sepsis mortality is FER rs4957796. However, it is not known how this variant is associated with bloodstream infection incidence and mortality. Methods We used prospective data from 1995–2017 from the population-based HUNT Study. Genotypes were ascertained from blood samples, and additional genotypes were imputed. Information on bloodstream infection and diagnosis codes at hospitalization were collected through record linkage with all hospitals in the area. Results A total of 69 294 patients were included. Patients with the rs4957796 CC genotype had an increased risk of developing a bloodstream infection compared with the TT genotype (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.00–1.43). However, there was a protective additive effect of the C allele in terms of mortality in the total study population (HR, 0.77; 95% CI, .64–.92 per copy of the C allele) and among bloodstream infection patients (odds ratio, 0.70; 95% CI, .58–.85 per copy of the C allele). The results did not appear to be affected by selection bias. Conclusions The rs4957796 CC genotype was associated with an increased risk of contracting a bloodstream infection but with a reduced risk of dying from one. The latter finding is in line with studies of sepsis case fatality, while the former expands our understanding of the immunoregulatory role of this polymorphism., The C allele of FER rs4957796 has been associated with reduced sepsis case fatality. In this prospective study of 69 294 patients, the C allele increases the risk of developing bloodstream infection but reduces the risk of dying from one.

Aims Extracellular matrix remodelling may influence atherosclerotic progression and plaque stability. We hypothesized that evaluation of extracellular matrix markers, with potentially different roles during atherogenesis, could provide information on underlying mechanisms and risk of myocardial infarction (MI) in apparently healthy individuals. Methods We conducted a case-control study nested within the population-based HUNT2 cohort in Norway. A total of 58,761 men and women, free of known cardiovascular disease, were followed for a first MI. During 11.3 years of follow-up, 1587 incident MIs were registered, and these cases were compared with 3959 age- and sex-matched controls. Circulating levels of the ECM proteins CD147 (ECM metalloproteinase inducer; EMMPRIN), cartilage oligomeric matrix protein (COMP: thrombospondin-5) and YKL-40 (chitinase-3-like-1) were measured by enzyme immunoassays. Results We found an inverse association between COMP (quartile (Q) 4 vs. Q1: hazard ratio 0.81 (95% confidence interval: 0.67-0.98)) and YKL-40 (Q4 vs. Q1: hazard ratio 0.77 (0.62-0.95)) with incidence of MI after full multivariable adjustment. Serum CD147 was not associated with MI risk in adjusted analysis. Conclusion High levels of COMP and YKL-40 were associated with lower risk of incident MI, suggesting a potential beneficial role in promoting plaque stability in individuals without incident cardiovascular disease.

Aims Interleukin-6 (IL-6) contributes to atherosclerotic plaque destabilization and is involved in myocardial injury during ischaemia–reperfusion. Interleukin-6 is therefore a potential therapeutic target in myocardial infarction (MI). We hypothesized that the IL-6 receptor antagonist tocilizumab would attenuate inflammation, and secondarily reduce troponin T (TnT) release in non-ST-elevation MI (NSTEMI). Methods and results In a two-centre, double-blind, placebo-controlled trial, 117 patients with NSTEMI were randomized at a median of 2 days after symptom onset to receive placebo (n = 59) or tocilizumab (n = 58), administered as a single dose prior to coronary angiography. High sensitivity (hs) C-reactive protein and hsTnT were measured at seven consecutive timepoints between Days 1 and 3. The area under the curve (AUC) for high-sensitivity C-reactive protein was the primary endpoint. The median AUC for high-sensitivity C-reactive protein during hospitalization was 2.1 times higher in the placebo than in the tocilizumab group (4.2 vs. 2.0 mg/L/h, P < 0.001). Also, the median AUC for hsTnT during hospitalization was 1.5 times higher in the placebo group compared with the tocilizumab group (234 vs. 159 ng/L/h, P = 0.007). The differences between the two treatment groups were observed mainly in (i) patients included ≤2 days from symptom onset and (ii) patients treated with percutaneous coronary intervention (PCI). No safety issues in the tocilizumab group were detected during 6 months of follow-up. Conclusion Tocilizumab attenuated the inflammatory response and primarily PCI-related TnT release in NSTEMI patients. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2016.

Objectives. Patients with inflammatory rheumatic diseases (IRDs) have a higher morbidity and mortality from accelerated atherosclerosis than the general population. We hypothesized that patients with the combination of IRD and coronary artery disease (CAD) would have a certain inflammatory phenotype compared with CAD patients without this comorbidity. Methods. Four groups of patients were included: patients with IRD, referred to coronary artery bypass grafting (CABG) (CAD–IRD, n = 67), patients without IRD, referred to CABG (CAD, n = 52), patients with IRD without CAD (IRD, n = 32) and healthy controls (n = 30). Plasma levels of several inflammatory markers were analysed by enzyme immunoassays. Results. (i) Plasma levels of markers of endothelial cell activation [i.e. vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor] and osteoprotegerin (OPG) were significantly increased and plasma levels of CCL21 significantly decreased in CAD–IRD patients as compared with CAD patients without IRD. (ii) Within the CAD–IRD group, acute coronary syndrome was a significant predictor of OPG, suggesting an enhanced inflammatory response during plaque destabilization in CAD–IRD patients. (iii) Plasma levels of VCAM-1, OPG and CCL21, but not lipid parameters, IRD characteristics and several other inflammatory markers (e.g. CRP), were significant predictors of CAD–IRD as opposed to CAD in two logistic regression models. Conclusion. Our findings further support a role for inflammation in the accelerated form of atherosclerosis in IRD patients, and suggest that certain inflammatory pathways, such as the enhanced endothelial cell activation and the RANK ligand/RANK/OPG system, may be of particular importance.

Aims Several studies suggest a pro-atherogenic role for the CC chemokine receptor 2 (CCR2), thought to reflect interaction with monocyte chemoattractant protein (MCP)-1. Based on its ability to attract leucocytes into inflamed tissue, we hypothesized a pro-atherogenic role for MCP-4, another CCR2 ligand. Methods and results Our main findings were: (i) patients with symptomatic carotid stenosis ( n = 29), but not those with asymptomatic plaques ( n = 31), had significantly raised plasma levels of MCP-4 compared with healthy controls ( n = 20); (ii) in vitro , releasate from activated platelets markedly increased the expression of MCP-4 and CCR2 in THP-1 monocytes, and enhanced the MCP-4-mediated effect on interleukin-8 secretion in these cells, involving the platelet-derived chemokine RANTES; (iii) while MCP-1 had no effect on the release of RANTES and interferon-inducible protein of 10 kDa in tumour necrosis factor α-pre-activated THP-1 monocytes, MCP-4 profoundly enhanced the release of these pro-atherogenic chemokines; and (iv) the data indicate an inflammatory interaction between RANTES and MCP-4, involving CCR2, and mRNA levels of these mediators were markedly up-regulated within symptomatic atherosclerotic carotid plaque ( n = 81). Conclusion Our findings suggest that the pro-atherogenic effects of CCR2 may not be restricted to interaction with MCP-1, but could also involve activation by MCP-4, being an inflammatory link between platelet and monocyte activation.

ObjectivesThiazolidinediones (TZDs) reduce insulin resistance, but also have pleiotropic properties including effects on inflammation. The balance between protective and proatherogenic effects may differ in various patient populations. We studied the effect of rosiglitazone on inflammatory markers in patients with metabolic syndrome (MetSyn).MethodsIn a cross-over randomized controlled trial, 23 subjects with MetSyn were assigned to treatment with rosiglitazone that was uptitrated from 4 mg/day for 6 weeks followed by 8 mg/day for 6 weeks or matching placebo for 12 weeks, and then to the opposite treatment for 12 weeks. Plasma levels of inflammatory and metabolic markers were measured during follow-up.ResultsOur main findings were i) compared to placebo, rosiglitazone significantly decreased the plasma levels of the naturally occurring interleukin (IL)1 inhibitor, IL1 receptor antagonist (IL1Ra; P=0.001), potentially reflecting inflammatory effects on the IL1 system; ii) parallel to this, rosiglitazone decreased plasma levels of IL10 (P=0.029) further suggesting inflammatory effects; iii) rosiglitazone decreased uric acid levels (P=0.001), and monocyte chemoattractant protein-1 (P=0.05) and C-reactive protein (P=0.06) tended to be lower after rosiglitazone than placebo, suggesting potential pro- and anti-inflammatory effects simultaneously and iv) in vitro, rosiglitazone enhanced IL1Ra and decreased IL1β in THP-1 monocytes, illustrating the complex effects of these medications, potentially exhibiting anti-inflammatory effects on the IL1 system in certain tissues or cells at least at certain concentrations.ConclusionOur findings suggest inflammatory effects on the IL1 system during rosiglitazone therapy in MetSyn. However, anti-inflammatory effects were also observed, and the net effect of TZDs in MetSyn should be further investigated.

Summary Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by defective immunoglobulin production and high frequency of bacterial infections, autoimmunity and manifestations of chronic inflammation. The homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 are associated with modulation of inflammatory responses. CVID patients have decreased proportions of CCR7+ T cells in peripheral blood and we hypothesized a further dysregulation of CCL19/CCL21/CCR7 in CVID. Serum levels of CCL19 and CCL21 were compared in CVID patients and controls. T cell expression of CCR7 was related to clinical characteristics in CVID patients. Spleens extirpated from CVID patients were analysed for expression of CCL19, CCL21 and CCR7. Peripheral blood mononuclear cells (PBMC) from CVID patients and controls were analysed for cytokine response on stimulation with CCL19 and CCL21. The main findings were: (i) CVID patients have raised serum levels of CCL19 and CCL21 independently of features of chronic inflammation; (ii) CCL19 and CCR7 have similar expression in spleens from CVID patients and controls, while CCL21 is variably down-regulated in spleens from patients; (iii) T cell expression of CCR7 is particularly low in patients characterized by chronic inflammation in vivo; and (iv) PBMC from CVID patients had attenuated cytokine response to stimulation with CCL19 and CCL21. CVID patients have raised circulatory levels of CCL19 and CCL21, and an attenuated cytokine response to stimulation with these chemokines. Because CCR7, CCL19 and CCL21 are key mediators balancing immunity and tolerance in the immune system, the abnormalities of these mediators might contribute to the profound immune dysregulation seen in CVID.

SummaryCCL19 and CCL21 and their receptor CCR7 are expressed constitutively within lymphoid organs, regulating lymphocyte homing. Recent studies suggest that these chemokines may have inflammatory properties. We hypothesized a role of CCL19/CCL21 in human immunodeficiency virus (HIV) infection by promoting inflammation. We examined the expression of CCL19 and CCL21 in mononuclear cells from peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) in HIV-infected patients before and during highly active anti-retroviral therapy (HAART). We also examined the ability of CCL19/CCL21 to promote inflammatory responses in these patients. PBMC from untreated HIV-infected patients (n = 29) released enhanced levels of CCL19 spontaneously compared with cells from controls (n = 20), particularly in those with symptomatic disease (n = 15, P

Aims This study assessed the relationship between inflammatory mediators and indices of infarct size and left-ventricular (LV) remodelling following successful primary percutaneous coronary intervention (PCI) in patients with first time ST elevation myocardial infarction (MI). Methods and results Forty-two patients admitted with an occluded single vessel were recruited consecutively. Cardiac magnetic resonance was used for serial assessment (2 days, 1 week, 2 months) of infarct size, microvascular obstruction (MO), and LV remodelling. Inflammatory mediators were analysed before and after PCI. Our major findings were: (1) Following PCI, there was a marked increase in plasma levels of C-reactive protein, closely correlated with an increase in interleukin-6 and terminal complement complex, reaching maximum 2 days after PCI; (2) C-reactive protein 2 days after PCI was significantly correlated with infarct size and parameters of LV remodelling 2 months after PCI; (3) Patients with persistent MO had significantly higher C-reactive protein levels 2 days following PCI. Conclusion We suggest that the rapid increase in C-reactive protein levels in this model of successful revascularization of a single, totally occluded vessel reflects the degree of inflammation within the infarcted area. Our findings support a role for C-reactive protein-mediated complement activation as both a marker and mediator of myocardial damage following MI. Clinical study no.: NCT 00465868.

Aims CXC ligand 16 (CXCL16) may be involved in inflammation and lipid metabolism, and we hypothesized a role for this chemokine in coronary artery disease (CAD). Methods and results We performed clinical studies in CAD patients as well as experimental studies in cells with relevance to atherogenesis [i.e. endothelial cells, vascular smooth muscle cells (SMC), and peripheral blood mononuclear cells (PBMC)]. We also examined the ability of HMG-CoA reductase inhibitors (statins) to modulate CXCL16 levels both in vivo and in vitro . Our main findings were: (i) patients with stable ( n = 40) and unstable ( n = 40) angina had elevated plasma levels of CXCL16 compared with controls ( n = 20); (ii) low-dose simvastatin (20 mg qd, n = 15) and high-dose atorvastatin (80 mg qd, n = 9) down-regulated plasma levels of CXCL16 during 6 months of therapy; (iii) in vitro , atorvastatin significantly decreased the interleukin (IL)-1β-mediated release of CXCL16 from PBMC and endothelial cells; (iv) attenuating effect of atorvastatin on the IL-1β-mediated release of CXCL16 in PBMC seems to involve post-transcriptional modulation as well as down-regulation of CXCL16 release through inhibition of the protease a disintegrin and metalloproteinase 10 (ADAM10); (v) soluble CXCL16 increased the release of IL-8, monocyte chemoattractant peptide 1, and matrix metalloproteinases in vascular SMC and increased the release of IL-8 and monocyte chemoattractant peptide 1 in PBMC, with particularly enhancing effects in cells from CAD patients. Conclusion Our findings suggest that soluble CXCL16 could be linked to atherogenesis not only as a marker of inflammation, but also as a potential inflammatory mediator.

Summary Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by different experimental approaches, including studies in peripheral blood and mononuclear cells (MNC) from bone marrow aspirates before and during highly active anti-retroviral therapy (HAART). We found that: before initiating HAART, HIV-infected patients (n = 37) had significantly decreased serum NGAL levels compared with healthy controls (n = 26); (ii) during HAART, there was a gradual and significant increase in NGAL concentrations reaching levels comparable to those in healthy controls after 12 months; (iii) this increase was seen primarily in virological responders to HAART (HIV RNA level

Aims Inflammatory cytokines may play a pathogenic role in heart failure (HF). CD40-CD40 ligand (CD40L) interactions are important in atherogenesis and based on its role in inflammation we sought to evaluate the role of CD40L in human HF. Methods and results Serum levels of soluble (s) CD40L were measured in 236 patients with acute HF following myocardial infarction, treated with either angiotensin-converting enzyme (ACE)-inhibition or angiotensin II blockade and followed for 2 years, and in 116 patients with chronic HF. Our main findings were: (i) patients with acute HF had increased sCD40L levels, particularly those with severe HF, diabetes, or hypertension; (ii) when these patients were followed longitudinally, persistently raised sCD40L levels were found throughout the observation period with no effect of captopril or losartan; (iii) the increase in sCD40L during follow-up was not seen in patients receiving warfarin therapy; (iv) patients with chronic HF also had raised sCD40L, significantly correlated with clinical severity, neurohormonal dysregulation, and left ventricular dysfunction; (v) studies from different blood compartments suggest that the vasculature of lower extremities and the failing myocardium itself may produce and secrete sCD40L in chronic HF. Conclusion Our findings may suggest a pathogenic role for enhanced CD40-CD40L interactions in human HF.

SUMMARYToll-like receptor 2 (TLR2) stimulation in monocytes may contribute to enhanced inflammation and viral replication in HIV infection. In the present study we examined if TLR2 stimulation could modulate chemokine responses in peripheral blood mononuclear cells (PBMC) from HIV-infected patients and healthy controls. Our main findings were, with similar qualitative patterns in both healthy controls and HIV-infected patients: (1) TLR2 stimulation induced up-regulation of several chemokines at the mRNA level as well as increased protein levels of macrophage inflammatory protein (MIP)-1α, interleukin (IL)-8 and regulated on activation, normal T cell expressed and secreted (RANTES); (2) TLR2 stimulation induced enhanced protein expression of CCR5 (a receptor for MIP-1α and RANTES) on monocytes; (3) In vitro stimulation with RANTES induced release of MIP-1α, MCP-1, IL-8 and interferon-γ from PBMC. While increased levels of β-chemokines possibly have antiviral effects, TLR2 stimulation may also promote a chemokine-driven inflammatory loop, potentially contributing to the immunopathogenesis of HIV infection.

Aims Inflammation plays an essential role in the atherosclerotic process, and chemokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) seem to play a pivotal role in the pathogenesis of atherosclerosis. A possible common inflammatory basis for the pathogenesis of type 2 diabetes, metabolic syndrome and atherosclerosis has been suggested. In this study we investigated the effect of physical exercise and the HMG-CoA reductase inhibitor pravastatin on peripheral markers of inflammation in subjects with the metabolic syndrome. Methods The study was an unmasked randomized 2×2 factorial trial of 12 weeks duration. Results In the combined exercise groups there was a significant reduction in MCP-1 and IL-8 of 48pg/ml ( P =0.04) and 1.0pg/ml ( P =0.007), respectively, as compared to the combined non-exercise groups. There was also a significant reduction vs baseline of 50pg/ml (33%) ( P =0.002) and 0.35pg/ml (13%) ( P =0.03) for MCP-1 and IL-8, respectively. Changes in MCP-1 were significantly correlated to changes in visceral fat ( r =0.41, P =0.02). Conclusion The protective effect of exercise might in part be due to suppression of the inflammatory process.

Objective: Inflammation may play a pathogenic role in chronic heart failure (CHF). The objective of the study was to characterise the imbalance in the cytokine network in CHF. Methods: cDNA expression arrays were used to analyse the gene expression of cytokines and related mediators in peripheral blood mononuclear cells (PBMC) from CHF patients ( n =8) and healthy controls ( n =8). Real-time quantitative reverse transcription–polymerase chain reaction (RT-PCR) was used to determine the gene expression of individual genes in additional 12 patients and eight controls. Results: From 375 genes, 34 were upregulated and two downregulated in CHF patients in the cDNA expression array experiments. Regulated genes included chemokines/-receptors, members of the transforming growth factor β superfamily, orphan receptors and in particular several members of the tumor necrosis factor (TNF) superfamily. Thus, 4-1BB ligand (L), APRIL, CD27L, CD40L, FasL, LIGHT, TRAIL-receptor 4 were upregulated, while TRAIL-receptor 3 was downregulated. Real-time quantitative RT-PCR confirmed significantly upregulated gene expression of APRIL, LIGHT, FasL and CD27L in CHF patients and showed in addition significantly enhanced gene expression of TNFα and TRAIL. Conclusion: The present study demonstrates differential gene expression in PBMC of several members of the cytokine network in CHF. In particular, the enhanced expression of several ligands in the TNF superfamily may reflect a potential pathogenic role of these cytokines in CHF.

Objectives: Chemokines regulate several biological processes, such as chemotaxis, collagen turnover, angiogenesis and apoptosis. Based on the persistent immune activation with elevated circulating levels of chemokines in patients with congestive heart failure (CHF), we have hypothesised a pathogenic role for chemokines in the development of CHF. The objective of this study was to examine mRNA levels and cellular localisation of chemokines and chemokine receptors in human CHF. Methods: We examined explanted hearts from ten patients with end-stage heart failure (all chambers) and in ten organ donors using an RNase protection assays and immunohistochemical techniques. Results: Our main findings were: (i) expression of eight chemokine and nine chemokine receptor genes in both failing and nonfailing myocardium, (ii) particularly high mRNA levels of monocyte chemoattractant protein (MCP)-1 and CXC-chemokine receptor 4 (CXCR4), in both chronic failing and nonfailing myocardium, (iii) decreased mRNA levels of MCP-1 and interleukin (IL)-8 in the failing left ventricles compared to failing left atria, (iv) decreased chemokine (e.g., MCP-1 and IL-8) and increased chemokine receptor (e.g., CCR2, CXCR1) mRNA levels in failing left ventricles and failing left atria compared to corresponding chambers in the nonfailing hearts and (v) immunolocalisation of MCP-1, IL-8 and CXCR4 to cardiomyocytes. Conclusion: The present study demonstrates for the first time chemokine and chemokine receptor gene expression and protein localisation in the human myocardium, introducing a new family of mediators with potentially important effects on the myocardium. The observation of chemokine dysregulation in human end-stage heart failure may represent a previously unknown mechanism involved in progression of chronic heart failure.

Objectives: The purpose of the present study was to examine the circulating levels of CXC-chemokines in patients with various degree of congestive heart failure (CHF). Background: CXC-chemokines may be important mediators in the persistent immune activation observed in CHF patients by activation of circulating neutrophils, T-cells and monocytes and possibly by the recruitment of these cells into the failing myocardium. Methods: Levels of interleukin (IL)-8, growth-regulated oncogene (GRO)α and epithelial neutrophil activating peptide (ENA)-78 were measured both in serum and in platelet-free plasma by enzyme immunoassay in 47 patients with CHF and in 20 healthy controls. Results: (i) CHF patients had significantly elevated levels of all the three CXC-chemokines with IL-8 and GROα showing a gradual increase along with increasing NYHA class. (ii) There was an inverse correlation between IL-8 and left ventricular ejection fraction (EF) and cardiac index (CI). (iii) Both unstimulated and lipopolysaccharide (LPS)-stimulated monocytes from CHF patients released markedly elevated amounts of all three CXC-chemokines. (iv) Platelets from patients with severe CHF were characterised by decreased content of GROα and ENA-78 as well as decreased release of these chemokines upon thrombin receptor stimulation. (v) Activated platelets stimulated peripheral blood mononuclear cells in vitro to enhanced release of IL-8, and neutralising antibodies against ENA-78 inhibited this interaction. Conclusions: This study demonstrates for the first time elevated levels of CXC-chemokines in CHF, which may be of importance for progression of heart failure. Our findings further suggest that activated monocytes and platelets may contribute to enhanced CXC-chemokine levels in CHF.

presence of myofibroblasts in all layers of the intestinal wall. Ulcerative colitis (UC) is classically considered to be a purely mucosal disease although rarely transmural complications such as strictures and stenosis develop. Fibrogenesis in UC has not been studied systematically yet and may be a neglected phenomenon. We therefore investigated whether there is a different fibrotic load in acute vs longstanding UC and whether the degree of fibrosis in UC correlates with the severity of inflammation. Methods: Colectomy specimens from all UC patients operated at the AMC between 2007 2012 were reviewed. Specimens from patients with recent onset refractory therapy UC (diagnosis 10 years) were selected. Patients operated for colon cancer without UC served as controls. On HE 29% vs 33% vs 54%, p = 0.009). Between acute and late UC there was no difference in collagen deposition, however between UC together and controls there was more collagen I expression in the mucosa, MM and muscularis externa (50% vs 10%, p = 0.02; 28% vs 10%, p = 0.048; 71% vs 20%, p = 0.003). In both early and long UC duration, we did not find a correlation between inflammation or collagen deposition or MM thickness. There was a negative correlation between inflammation and aSMA positivity in the submucosa (R = 0.51, p = 0.003) and MM (R = 0.37, p = 0.04). Conclusions: In our series of colectomy specimens, there is more collagen deposition in UC than in controls. No association between disease duration and increased collagen deposition could be found. Expression of aSMA however is lower in UC and correlates with inflammation. Fibrosis in UC does not appear to increase significantly over time.

presence of myofibroblasts in all layers of the intestinal wall. Ulcerative colitis (UC) is classically considered to be a purely mucosal disease although rarely transmural complications such as strictures and stenosis develop. Fibrogenesis in UC has not been studied systematically yet and may be a neglected phenomenon. We therefore investigated whether there is a different fibrotic load in acute vs longstanding UC and whether the degree of fibrosis in UC correlates with the severity of inflammation. Methods: Colectomy specimens from all UC patients operated at the AMC between 2007 2012 were reviewed. Specimens from patients with recent onset refractory therapy UC (diagnosis 10 years) were selected. Patients operated for colon cancer without UC served as controls. On HE 29% vs 33% vs 54%, p = 0.009). Between acute and late UC there was no difference in collagen deposition, however between UC together and controls there was more collagen I expression in the mucosa, MM and muscularis externa (50% vs 10%, p = 0.02; 28% vs 10%, p = 0.048; 71% vs 20%, p = 0.003). In both early and long UC duration, we did not find a correlation between inflammation or collagen deposition or MM thickness. There was a negative correlation between inflammation and aSMA positivity in the submucosa (R = 0.51, p = 0.003) and MM (R = 0.37, p = 0.04). Conclusions: In our series of colectomy specimens, there is more collagen deposition in UC than in controls. No association between disease duration and increased collagen deposition could be found. Expression of aSMA however is lower in UC and correlates with inflammation. Fibrosis in UC does not appear to increase significantly over time.