[Case report: persistent fever after SARS-CoV-2 infection]. / Fallbericht: Persistierendes Fieber nach SARS-CoV-2-Infektion.

A 44-year-old man had persistent fever following a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Because of progressive sinus tachycardia, thyroid hormones were measured which showed hyperthyroidism. Thyroid sonography revealed enlargement of the thyroid gland with hypoechoic areas with blurred margins. We diagnosed subacute granulomatous thyroiditis associated with SARS-CoV­2 infection and initiated therapy with prednisolone. This therapy resulted in rapid improvement of the patient's clinical condition and complete remission after three months.

The amount of liver tissue is essential for accurate histological staging in patients with autoimmune hepatitis.

The gold standard for the evaluation of liver fibrosis is histology. However, the heterogenous distribution of fibrosis limits the sensitivity of histology. The collection of two samples with a 16G needle is therefore recommended to reduce the risk of sampling error. The aim of this study was to investigate whether this standard is also applicable to patients with autoimmune hepatitis (AIH). This retrospective study included patients with AIH, who underwent mini-laparoscopic biopsy at our center between 2011 and 2020 (n = 32). Diagnosis was verified by usage of the simplified AIH score (≥ 6). Patients were categorized into three groups, based on the number of portal fields (PF) in the collected liver tissue (< 10 PF, 10 - 19 PF, ≥ 20 PF). We correlated the histological staging for these groups with the mini-laparoscopic fibrosis score (MLFS). Furthermore, non-invasive methods for the assessment of fibrosis were correlated with the histological staging (acoustic radiation force impulse (ARFI) and FIB-4 score). MLFS correlated well with histological staging (r = 0.649, p = 0.0001). The correlation between MLFS and histology improved with higher numbers of histologically analyzed portal fields (< 10 PF: r = 0.400, p = 0.378; 10 - 19 PF: r = 0.5467, p = 0.023; ≥ 20 PF: r = 0.956, p = 0.0002). The probability of collecting at least 10 or 20 portal fields was dependent on the number and diameter of the samples. For all patients with at least two 16G biopsies, 10 or more PF were available. With three 16G biopsies, at least 20 PF were obtained for all patients. ARFI correlated with MLFS and histological staging only in patients with low/moderate-grade inflammation as defined by ALT < 10xULN (upper limit of normal) (MLFS: r = 0.723; p = 0.004; histology: r = 0.619, p = 0.018). FIB-4 did not correlate with histological staging. The amount of liver tissue obtained by liver biopsy is crucial to minimalize the risk of sampling error and thus underestimation of fibrosis. This study was the first to investigate the amount of liver tissue required for histological staging in AIH. Our data suggest that diagnostic accuracy is likely to be higher with 20 PF compared to the generally recommended 10 PF. We therefore recommend to perform three biopsies with a 16G needle in (suspected) AIH patients. ARFI correlated well with histological staging unless inflammatory activity is high.

Cytokines in inflammatory bowel diseases - Update 2020.

Inflammatory Bowel Diseases (IBD), namely Crohn's Disease and Ulcerative Colitis, cause a significant disease burden in modern civilization. Ever since the introduction of anti-TNF-directed therapies 20 years ago, cytokines have attracted a lot of research attention and several cytokine-directed therapies have been implemented in the clinical treatment of these diseases. The research progress in these past years has underlined the importance of both myeloid and lymphoid elements of the immune system in the pathogenesis of IBD and their cytokine-mediated interplay. The conceptual framework of the mucosal cytokine network has shifted during these years from a T helper (Th) dichotomy (Th1/Th2) to the effector/regulatory T cell balance, while nowadays, the importance of myeloid cell instruction of lymphocytes, namely by IL-12 and IL-23, is increasingly recognized. Anti-IL-12p40 agents, like ustekinumab, groundbreakingly changed patient care, and anti-IL23p19-directed approaches are on the verge of grand success. In this review we present a modular approach to understand the cytokine network and put it into the context of the pathogenesis of IBD with a special focus on publications since 2014.

Correction to: Influence of cancer and acute inflammatory disease on taste perception: a clinical pilot study.

The Acknowledgement Statement was incorrect in the original publication of this article [1] and the previous correction note [2]. The correct statement is as follows.

Beyond the border: the use of lenvatinib in advanced hepatocellular carcinoma after different treatment lines: a retrospective analysis.

The systemic treatment of unresectable hepatocellular carcinoma (HCC) has been improved throughout the past years. Different tyrosine kinase inhibitors (TKI) and checkpoint inhibitors have approval for first- and second-line treatment. Still, data are missing about the choice for the right agent and senseful therapy sequences. Between 2017 and 2019 we treated 149 HCC patients. From those, we identified the patients, who received lenvatinib either as a first-line treatment or in a later treatment line. We investigated seven patients retrospectively, who received lenvatinib in second, third, or fourth treatment line regarding efficacy and safety. Besides that, we compared those patients with 13 patients, who received lenvatinib as a first-line treatment regarding duration of therapy, overall survivial (OS), side effects and best response to treatment. We discovered remission (PR) showed 4/7, stable disease (SD) 2/7 and 1/7 mixed response with an overall tolerable safety profile in patients with a later line lenvatinib treatment. The duration and overall survival for therapy is similar in first- and later treatment lines with comparable results. Most side effects are moderate in each treatment line. Remarkably, on patient diagnoses with HCC (the Barcelona Clinic Liver Cancer C algorithm), who received lenvatinib in fourth line reached 67 months OD since diagnosis. We conclude, that lenvatinib could be considered as a treatment option of HCC for later treatment lines.

Multicenter analysis of endoclot as hemostatic powder in different endoscopic settings of the upper gastrointestinal tract.

Gastrointestinal bleeding (GIB) still presents a demanding situation with high morbidity and mortality rates; thus hemostatic powders such as EndoClot (EC) have been developed to improve endoscopic armament. The aim of the present study was to determine which indications triggered the application of EC and to assess resulting hemostasis rates. Forty three patients undergoing endoscopical procedures in three hospitals; two tertiary care and one university hospital, were included. EC was applied in 48 endoscopies in 43 patients (27 male, age 65.5 years, range 28 - 92 years) following four different indications. EC was used in active GIB as rescue or first-line therapy giving a short-term and long-term hemostasis in 13/17 patients (76.5%). In the setting of non-active GIB, following conventionally achieved hemostasis or endoscopic interventions, EC was found to prevent bleeding in 19/21 patients (90.4%). EC induced hemostasis in 8/10 patients (80%) with impaired coagulation. EC failures resulted from tumor bleeding, Forrest I lesions or perforated duodenal ulcers. No major adverse events were recorded and one technical failure (2.1%) occurred. EC was applied as first line or salvage treatment in ongoing bleedings with promising results. Furthermore, EC was used after successful hemostasis or following endoscopic interventions to further reduce re-bleeding rates. We saw promising results in all indications, albeit lacking a control group.

Correction to: Influence of cancer and acute inflammatory disease on taste perception: a clinical pilot study.

The "Acknowledgment Statement" of the published paper is incorrect. The correct statement should be the below: Acknowledgements We thank Sarah Vogel for her support in taste test realization and Yvonne Sauermann for preparation of the tastant solutions. The present work was carried out by Ms. Schalk in order to meet the requirements for the awarding of the title of Dr. med. at the FAU.

[Inflammatory bowel diseases : Crohn's disease and ulcerative colitis]. / Chronisch-entzündliche Darmerkrankungen : Morbus Crohn und Colitis ulcerosa.

Inflammatory bowel diseases (IBD) are complex diseases. Epidemiological studies suggest rising incidences in industrialized countries. The article is based on a literature search in PubMed and is oriented on the current guidelines published by the European Crohn's and Colitis Organisation. IBD are characterized by chronic diarrhoea, abdominal pain and peranal haemorrhage. Extraintestinal manifestations commonly affect joints, skin, eyes and bile tracts. Early diagnosis and therapeutic intervention determine individual patient outcome. Medical treatment currently includes aminosalicylates, corticosteroids, thiopurines, calcineurin inhibitors and biologicals. IBDs require anti-inflammatory and if necessary immunosuppressive therapy. Due to extraintestinal complications and the possible need for surgical intervention, an interdisciplinary approach is important.

Acoustic radiation force impulse (ARFI) elastography of the bowel wall as a possible marker of inflammatory activity in patients with Crohn's disease.

AIM: To evaluate acoustic radiation force impulse (ARFI) shear-wave velocities of the bowel wall in patients with Crohn's disease (CD). MATERIAL AND METHODS: ARFI shear-wave elastography was analysed within the wall of the stomach, terminal ileum, and sigmoid, and correlated with ultrasound signs of activity in CD patients both retrospectively and in a prospective cohort. RESULTS: A total of 77 retrospective and 21 prospective CD patients were included. ARFI elastography in the stomach, the normal ileum, and sigmoid was lower than in ileitis or sigmoiditis. Retrospectively, the ARFI values correlated with the bowel wall thickness and Limberg vascularisation score. Prospectively, there was no correlation between ARFI and bowel wall thickness, Limberg score, clinical activity, or C-reactive protein. A cut-off analysis of 105 ileal ARFI measurements showed a cut-off value of 1.92 m/s for the diagnosis of ileal inflammation with 75.3% sensitivity and 87.5% specificity. CONCLUSION: In patients with CD, ARFI shear-wave velocities show a trend to higher values in inflamed bowel wall thickening on B-mode ultrasound; however, the differences appear small and may not be clinically significant. The factors influencing ARFI measurements of the bowel wall require further investigation.

Influence of cancer and acute inflammatory disease on taste perception: a clinical pilot study.

PURPOSE: Cancer patients are at high risk of malnutrition and tumor cachexia further increasing morbidity and mortality. Reasons for cachexia are not clear yet, but inflammatory processes as well as the occurrence of taste disorders reducing nutrient uptake are discussed to play key roles. The purpose of this study was to gain insight into causative factors of taste disturbance in cancer patients. Does the cancer itself, inflammatory processes or cancer therapy influence taste disorders? METHODS: To capture an underlying taste disorder patients with cancer (n = 42), acutely hospitalized inflammatory disease patients (n = 57) and healthy controls (n = 39) were examined. To assess the influence of chemotherapy, patients with and without chemotherapy were compared. Taste tests were performed according to DIN ISO 3972:2011. Inflammation was recorded using laboratory parameters. Statistical evaluation was conducted using the Software R. RESULTS: Cancer patients showed significantly increased taste thresholds for sweet, salty, and umami compared to healthy controls. There were no significant differences in taste detection and recognition between patients with former, current, or without chemotherapeutical treatment. Patients with an acute inflammatory disease showed an increased taste threshold for umami compared to healthy controls. CONCLUSIONS: It could be shown that cancer patients suffer from taste disorders irrespective of an existing chemotherapeutical treatment. Cancer-related inflammation appears to have a greater impact on taste perception than an acute inflammatory process. Therefore, an adapted dietary adjustment should be carried out at an early stage for cancer patients in order to avoid nutritional disorders caused by a taste disorder.

Safety and efficacy of intravenous cyclophosphamide pulse therapy in therapy refractory Crohn's disease patients.

A major challenge in the management of persistently active Crohn's disease patient's refractory to treatment regimen following the current guidelines is the induction of remission, which is a prerequisite for subsequent maintenance therapy. The aim of this study was to evaluate both the clinical and endoscopic benefit of intravenous cyclophosphamide pulse therapy in patients with active and therapy refractory Crohn's disease. Nine patients with acute moderate to severe Crohn's disease, not responding to conventional as well as biological therapy regimen received 3 - 9 cycles of monthly treatments with intravenous cyclophosphamide (680 - 1000 mg) in an uncontrolled setting and were retrospectively analyzed. Eight of nine patients (88.9%) had a clinical response (measured by a decrease in the Harvey-Bradshaw index, HBI ≥ 3) and two of nine patients (22.2%) achieved clinical remission (HBI ≤ 4) at week 8 after two applications of intravenous cyclophosphamide therapy. These response and remission rates remained unchanged after individual completion of cyclophosphamide therapy. Median HBI decreased from 18 (7 - 25) at the beginning of therapy to 7 (3 - 18) at week 8. 5 of 9 patients (56%) showed endoscopic response (defined by a reduction of ulcers) and one patient (11%) reached endoscopic remission (defined by the absence of ulcers) after the last application of cyclophosphamide. Arthralgia, which was present in 4 of 9 (44%) patients, was unchanged in most patients after cyclophosphamide therapy, although one patient described a marked reduction in joint pain. Cyclophosphamide pulse therapy was well tolerated during the whole treatment course in all subjects. One patient with long-standing Crohn's disease was diagnosed with a high-grade intraepithelial neoplasia in the rectum and underwent surgical intervention, where the diagnosis of an early stage adenocarcinoma was made. We concluded that intravenous cyclophosphamide pulse therapy was well tolerated by most patients and effective for inducing clinical and endoscopic response and remission in patients with therapy refractory Crohn's disease. In patients who are unresponsive to available therapies, including available biological treatment options, cyclophosphamide therefore represents a potential option to induce therapeutic response, which must then be maintained by other treatment modalities.

Diagnostic accuracy and interobserver variability of Dynamic Vascular Pattern (DVP) in primary liver malignancies - A simple semiquantitative tool for the analysis of contrast enhancement patterns.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a valuable tool in the diagnostic approach of focal liver lesions, but occasionally subjective and observer-dependent. Semiquantitative evaluation of dynamic CEUS (DCEUS) with standardised software programmes such as Dynamic Vascular Pattern (DVP) could help to improve diagnostic accuracy and objectivity in liver tumour assessment. OBJECTIVES: The present study aimed at evaluation of diagnostic accuracy of DVP in a clinical setting. MATERIALS AND METHODS: DVP images of 52 focal liver lesions [30 hepatocellular carcinomas (HCCs), 15 intrahepatic cholangiocellular carcinomas (ICCs), 7 focal nodular hyperplasias (FNHs)] were analysed by four blinded observers with different levels of CEUS-experience. Diagnostic accuracies for the assessment of dignity and entity were evaluated. RESULTS: Mean sensitivity, specificity, positive and negative predictive value for detection of malignancy with DVP were 48.4% /67.8% /92.7% and 29.3%, respectively. Total diagnostic accuracies for dignity/entity were 63.9% /38.5% (HCC: 58.3% /25.8%; ICC: 73.3% /50%; FNH: 67.9% /67.9%). Interreader-agreement was moderate (κ= 0.42-0.58). Differential diagnosis between ICC and HCC was most challenging. CONCLUSION: Although developed to improve diagnostic accuracy and objectivity in the assessment of focal liver lesions, DVP alone seems insufficient for differential diagnosis of HCC, ICC and FNH and cannot replace the skills of an experienced observer.

In-vivo multispectral video endoscopy towards in-vivo hyperspectral video endoscopy.

For in-vivo diagnostics of cancer and pre-cancer in the stomach, there is no endoscopic procedure offering both high sensitivity and high specificity. Our data suggest that multispectral or hyperspectral imaging may be helpful to solve this problem. It is successfully applied to the detection and analysis of easily reachable carcinomas, ex-vivo samples of hollow organ mucosal carcinomas and also histological samples. An endoscopy system which allows flexible multispectral videoendoscopy for in-vivo diagnostics has so far been unavailable. To overcome this problem, we modified a standard Olympus endoscopy system to conduct in-vivo multispectral imaging of the upper GI tract. The pilot study is performed on 14 patients with adeno carcinomas in the stomach. For analysis, Support Vector Machine with linear and Gaussian Kernel, AdaBoost, RobustBoost and Random-Forest-walk are used and compared for the data classification with a leave-one-out strategy. The margin of the carcinoma for the training of the classifier is drawn by expert-labeling. The cancer findings are cross-checked by biopsies. We expect that the present study will help to improve the further development of hyperspectral endoscopy and to overcome some of the problems to be faced in this process.

Outcome, comorbidity, hospitalization and 30-day mortality after closure of acute perforations and postoperative anastomotic leaks by the over-the-scope clip (OTSC) in an unselected cohort of patients.

BACKGROUND: Acute gastrointestinal (GI) wall defects contain a high risk of morbidity and mortality and may be closed endoscopically by a full-thickness over-the-scope clip (OTSC). METHODS: Unselected consecutive patients presenting with acute non-surgical perforations or postoperative anastomotic leaks or perforations underwent attempted OTSC placement as primary closure method after interdisciplinary consensus in three tertiary referral centres. Their clinical data and intervention characteristics were evaluated in an intention to treat analysis during a 24-month period to assess closure rates, 30-day mortality, hospitalization and comorbidity. RESULTS: In total, 34 patients (16 females, 18 males, 69.5 years) were included with 22 non-surgical perforations and 12 postoperative anastomotic leaks or perforations. Definitive closure of the perforations and leaks was achieved in 26/34 patients (76.5 %). Successful closure of the GI wall defect resulted in a significantly shorter hospital stay (8 days, p = 0.03) and was significantly correlated with comorbidity (r = 0.56, p = 0.005). In the group with OTSC failure, hospitalization was 18 days and 6 of 8 patients (75 %) required immediate surgery. Three deaths occurred in the group with successful OTSC closure due to comorbidity, while one death in the OTSC failure group was related to a refractory perforation. Favourable indications and locations for a successful OTSC procedure were identified as PEG complications, endoscopic or postoperative leaks of stomach, colon or rectum, respectively. CONCLUSIONS: In unselected patients, OTSC was effective for closure of acute GI wall defects in more than 75 % of all patients. Clinical success and short hospitalization were best achieved in patients without comorbidity, but closure of the perforation or the anastomotic leak was found to be not the only parameter relevant for patient outcome and mortality.

Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study.

BACKGROUND: Vedolizumab, a monoclonal antibody targeting the α4ß7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials. AIM: To determine the long-term effectiveness of vedolizumab in a real-world clinical setting. METHODS: This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI ≤ 4/pMayo ≤ 1) at week 54. Secondary endpoints included clinical response rates (HBI/pMayo score drop ≥3) and steroid-free clinical remission at weeks 30 and 54. RESULTS: Vedolizumab was stopped in 69/127 (56%) patients after a median time of 18 weeks (range 2-49) predominantly owing to lack or loss of response. Using nonresponder imputation analysis, clinical remission and steroid-free remission rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis, respectively. Lack of clinical remission was associated with prior treatment with anti-TNF or with steroids for more than 3 months in the last 6 months in ulcerative colitis. At week 14, the absence of remission in Crohn's disease or nonresponse in ulcerative colitis indicated a low likelihood of clinical remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted remission at week 54. CONCLUSION: Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21-25% after 54 weeks.

LI-RADS-CEUS - Proposal for a Contrast-Enhanced Ultrasound Algorithm for the Diagnosis of Hepatocellular Carcinoma in High-Risk Populations.

Purpose: To develop a contrast-enhanced ultrasound algorithm (LI-RADS-CEUS = liver imaging reporting and data system with contrast-enhanced ultrasound) for the diagnosis of hepatocellular carcinoma (HCC) in patients at risk. Materials and Methods: A CEUS algorithm (LI-RADS-CEUS) was designed analogously to CT- and MRI-based LI-RADS. LI-RADS-CEUS was evaluated retrospectively in 50 patients at risk with confirmed HCC or non-HCC lesions (test group) with subsequent validation in a prospective cohort of 50 patients (validation group). Results were compared to histology, CE-CT and CE-MRI as reference standards. Results: Tumor diagnosis in the test group/validation group (n = 50/50) were 46/41 HCCs, 3/3 intrahepatic cholangiocellular carcinomas (ICCs) and 1/6 benign lesions. The diagnostic accuracy of LI-RADS-CEUS for HCC, ICC and non-HCC-non-ICC-lesions was 89 %. For the diagnosis of HCC, the diagnostic accuracy was 93.5 % (43/46 cases) in the test group and 95.1 % (39/41 cases) in the validation group. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 94.3 %, 66.6 %, 94.3 % and 66.6 %, respectively (mean values from both cohorts). Histological findings of HCC were available in 40 versus 23 cases (in total: G1 / G2/G3: 15/35/13). Arterial hyperenhancement was seen in 68/87 (78.2 %) of HCCs. Arterial hyperenhancement with subsequent portal venous or late phase hypoenhancement was seen in 66 % of HCCs. Conclusion: LI-RADS-CEUS offers a CEUS algorithm for standardized assessment and reporting of focal liver lesions in patients at risk for HCC. Arterial hyperenhancement in CEUS is the key feature for the diagnosis of HCC in patients at risk, whereas washout is not a necessary prerequisite.

Comparison of Acoustic Radiation Force Impulse (ARFI) Elastography Measurements with the 4C1 Transducer to the 6C1HD Transducer: A Phantom and Patient Study.

Purpose: The aim of this study was to evaluate whether acoustic radiation force impulse (ARFI) elastography done with the 4C1 probe yields comparable results to the recently introduced 6C1HD probe. Materials and Methods: Measurements with the 4C1 and 6C1HD probes (Acuson S2000) were performed and compared in four different inclusions of an elasticity phantom model (QA049 CIRS) as well as in the liver of healthy individuals and patients with liver cirrhosis. Results: Measurements with the 6C1HD probe were slightly higher in all phantom inclusions (8, 14, 45, 80kPA) with a mean of 1.48 m/s (95 %-CI; 1.47 - 1.49), 2.18 m/s (95 %-CI; 2.17 - 2.19), 3.61 m/s (95 %-CI; 3.57 - 3.64) and 4.34 m/s (95 %-CI; 4.29 - 4.39) compared to the 4C1 transducer with 1.46 m/s (95 %-CI; 1.45 - 1.47), 2.15 m/s (95 %-CI; 2.14 - 2.16), 3.39 m/s (95 %-CI; 3.37 - 3.41) and 3.98 m/s (95 %-CI; 3.75 - 4.21), respectively (p = 0.04, p < 0.01, p < 0.01, p < 0.01). Cirrhotic patients (n = 40) had a higher mean shear wave speed with 3.00 m/s (95 %-CI; 2.80 - 3.21) with the 6C1HD transducer compared to 2.81 m/s (95 %-CI; 2.64 - 2.99) with the 4C1 transducer (p = 0.03). Healthy individuals (n = 20) had a mean shear wave speed of 1.12 m/s (95 %-CI; 1.06 - 1.17) with the 6C1HD probe and 1.12 m/s (95 %-CI; 1.05 - 1.19) with the 4C1 probe (p = 0.96). Conclusion: ARFI values assessed with a 6C1HD transducer are slightly higher than measurements with a 4C1 transducer in an ARFI phantom and in patients with liver cirrhosis. As the difference is small, current cut-off values keep their usefulness but should be interpreted with caution if measurements are close to the cut-off.

Transient receptor potential melastatin 8 ion channel in macrophages modulates colitis through a balance-shift in TNF-alpha and interleukin-10 production.

The transient receptor potential (TRP) ion channel family is well characterized in sensory neurons; however, little is known about its role in the immune system. Here we show that the cold-sensing TRPM8 has an unexpected role in innate immunity. TRPM8 expression and function in macrophages were demonstrated in vitro using molecular techniques and calcium imaging. In addition, adoptive macrophage transfer and systemic interleukin (IL)-10 overexpression were performed in experimental colitis. TRPM8 activation induced calcium-transients in murine peritoneal macrophages (PM) and bone marrow-derived macrophages of wild-type (WT) but not TRPM8-deficient mice. TRPM8-deficient PM exhibited defective phagocytosis and increased motility compared with those in WT, whereas the opposite effects of TRPM8 activation were induced in WT PM. TRPM8 activation or blockage/genetic deletion induced a anti- or pro-inflammatory macrophage cytokine profile, respectively. WT mice treated with repeated menthol (TRPM8 agonist) enemas were consistently protected from experimental colitis, whereas TRPM8-deficient mice showed increased colitis susceptibility. Adoptive transfer of TRPM8-deficient macrophages aggravated colitis, whereas systemic IL-10 overexpression rescued this phenotype. TRPM8 activation in peptidergic sensory neurons did not affect neuropeptide release from the inflamed colon. TRPM8 in macrophages determines pro- or anti-inflammatory actions by regulating tumor necrosis factor-α and interleukin-10 production. These findings suggest novel TRPM8-based options for immunomodulatory intervention.