• Crohn’s disease
• Enteric nervous system
• inflammation
• inflammatory bowel disease
• neuro-immune
• neuroprotection
• plexitis
• ulcerative colitis

• COVID-19
• Contributing factors
• Coronavirus
• Crohn’s disease
• Immune system dysfunction
• Inflammatory bowel disease
• LRDI
• Pandemic
• SARS-CoV
• SARS-CoV-2
• Severe acute respiratory syndrome
• Ulcerative colitis

• Cholinergic anti-inflammatory pathway
• Fetal complications
• Inflammation
• Nicotinic acetylcholine receptors
• Placenta
• Preeclampsia

• Cohort
• Knee replacement
• Osteoarthritis
• Smoking

• Patient education
• Patient reported outcome
• Patient satisfaction
• Rapid recovery
• Rehabilitation

Inflammatory bowel disease (IBD) is the collective term for chronic immune-mediated diseases of unknown, multifactorial etiology, arising from the interplay between genetic and environmental factors and including two main disease manifestations: ulcerative colitis (UC) and Crohn’s disease. In the last few decades, naturally occurring alkaloids have gained interest because of their substantial anti-inflammatory effects in several animal models of disease. Studies on mouse models of IBD have demonstrated the anti-inflammatory action of the main tobacco alkaloid, nicotine. In addition, anatabine, a minor tobacco alkaloid also present in peppers, tomato, and eggplant presents anti-inflammatory properties in vivo and in vitro. In this study, we aimed to evaluate the anti-inflammatory properties of nicotine and anatabine in a dextran sulfate sodium (DSS) mouse model of UC.

Oral administration of anatabine, but not nicotine, reduced the clinical symptoms of DSS-induced colitis. The result of gene expression analysis suggested that anatabine had a restorative effect on global DSS-induced gene expression profiles, while nicotine only had limited effects. Accordingly, MAP findings revealed that anatabine reduced the colonic abundance of DSS-associated cytokines and increased IL-10 abundance.

Our results support the amelioration of inflammatory effects by anatabine in the DSS mouse model of UC, and suggest that anatabine constitutes a promising therapeutic agent for IBD treatment.

• Colitis
• Mouse model
• Nicotine
• Plant-derived alkaloid

Smoking has detrimental effects on Crohn’s disease (CD) activity while data on ulcerative colitis (UC) are conflicting. Little is known about the use and impact of alternative smoking products in inflammatory bowel diseases (IBD).

To understand the patients’ perceptions of the impact of smoking on their IBD and to assess differences between CD and UC patients.

The questionnaire was developed by Philip Morris Products SA in cooperation with European Federation of Crohn's and Ulcerative Colitis Associations. The final survey questionnaire consisted of 41 questions divided in 8 categories: (1) Subject screener; (2) Smoking history; (3) Background information; (4) IBD disease background; (5) Current disease status; (6) Current therapeutics and medications; and (7) Current nicotine/cigarettes use and awareness of the impacts of smoking on IBD. The questionnaire was submitted online from 4^th November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative Colitis Associations website to IBD patients who were current smokers or had a history of smoking.

In total 1050 IBD patients speaking nine languages participated to the survey. Among them, 807 (76.9%) patients declared to have ever smoked or consumed an alternative smoking product, with a higher proportion of current cigarette smokers among CD patients (CD: 63.1% vs UC: 54.1%, P = 0.012). About two-thirds of the participants declared to have ever stopped cigarette smoking and restarted (67.0%), with a significantly higher proportion among UC patients compared to CD patients (73.1% vs 62.0%, P = 0.001). We also found significant differences between CD and UC patients in the awareness of the health consequences of smoking in their disease and in the perceived impact of smoking on disease activity, for both cigarettes and alternative smoking products.

This survey found significant differences between CD and UC patients in both awareness and perception of the impact of smoking on their disease. Further efforts should be done to encourage smoking cessation for all IBD patients, including UC patients.

• Inflammatory bowel disease
• Ulcerative colitis
• Crohn's disease
• Cigarettes
• Alternative smoking products
• Tobacco
• Nicotine
• Marijuana

• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/epidemiology
• Colitis, Ulcerative/therapy
• Crohn Disease/diagnosis
• Crohn Disease/epidemiology
• Humans
• Inflammatory Bowel Diseases
• Risk Factors
• Smoking/adverse effects
• Surveys and Questionnaires

• Improve
• Obstetrics
• Outcome
• PBM
• PPH
• Patient blood management
• Perinatal haemorrhage
• Pregnancy

• Blood Transfusion/methods
• Female
• Humans
• Obstetrics/methods
• Postpartum Hemorrhage/therapy
• Pregnancy
• Risk Factors

• Vifor Pharma

• Anti-inflammatory reflex
• Inflammation
• Kidney injury
• Neuroimmunomodulation
• Vagus

• Arthritis, Infectious/pathology
• Arthritis, Rheumatoid/pathology
• Cognitive Behavioral Therapy
• Humans
• Joint Diseases/pathology
• Osteoarthritis/pathology
• Quality of Life
• Randomized Controlled Trials as Topic
• Smoking/adverse effects
• Smoking Cessation/methods
• Spondylarthritis/pathology

• Consensus
• Crohn’s disease
• Evidence
• Guidelines
• Inflammatory bowel disease
• Ulcerative colitis

• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/epidemiology
• Colitis, Ulcerative/physiopathology
• Colitis, Ulcerative/therapy
• Consensus
• Crohn Disease/diagnosis
• Crohn Disease/epidemiology
• Crohn Disease/physiopathology
• Crohn Disease/therapy
• Early Detection of Cancer
• Humans
• Japan
• Proctocolectomy, Restorative
• Risk Factors

Clinical manifestations of inflammatory bowel disease (IBD) are not locally restricted to the gastrointestinal tract, and a significant portion of patients have involvement of other organs and systems. The visual system is one of the most frequently affected, mainly by inflammatory disorders such as episcleritis, uveitis and scleritis. A critical review of available literature concerning ocular involvement in IBD, as it appears in PubMed, was performed. Episcleritis, the most common ocular extraintestinal manifestation (EIM), seems to be more associated with IBD activity when compared with other ocular EIMs. In IBD patients, anterior uveitis has an insidious onset, it is longstanding and bilateral, and not related to the intestinal disease activity. Systemic steroids or immunosuppressants may be necessary in severe ocular inflammation cases, and control of the underlying bowel disease is important to prevent recurrence. Our review revealed that ocular involvement is more prevalent in Crohn’s disease than ulcerative colitis, in active IBD, mainly in the presence of other EIMs. The ophthalmic symptoms in IBD are mainly non-specific and their relevance may not be recognized by the clinician; most ophthalmic manifestations are treatable, and resolve without sequel upon prompt treatment. A collaborative clinical care team for management of IBD that includes ophthalmologists is central for improvement of quality care for these patients, and it is also cost-effective.

• Inflammatory bowel disease
• Crohn’s disease
• Ulcerative colitis
• Ocular complications
• Eye manifestations

• Gastroenterologists/organization & administration
• Immunosuppressive Agents/therapeutic use
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/epidemiology
• Intersectoral Collaboration
• Ophthalmologists/organization & administration
• Patient Care Team/organization & administration
• Prevalence
• Recurrence
• Scleritis/drug therapy
• Scleritis/epidemiology
• Scleritis/etiology
• Uveitis/drug therapy
• Uveitis/epidemiology
• Uveitis/etiology

• Crohn’s disease
• Diet
• Environment
• Smoking
• Ulcerative colitis

• Diet/adverse effects
• Dietary Supplements
• Enteral Nutrition/methods
• Environment
• Humans
• Inflammatory Bowel Diseases/etiology
• Inflammatory Bowel Diseases/therapy
• Risk Factors
• Sleep Wake Disorders/complications
• Smoking/adverse effects
• Stress, Psychological/complications

• K23 DK097142 NIDDK NIH HHS
• P30 DK043351 NIDDK NIH HHS

• pouchitis
• ulcerative colitis
• familial adenomatous polyposis
• rna sequencing
• ileal pouch

• Crohn disease
• Extraintestinal manifestations
• Inflammatory bowel disease
• Routine health maintenance
• Ulcerative colitis

• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/physiopathology
• Colitis, Ulcerative/therapy
• Crohn Disease/diagnosis
• Crohn Disease/physiopathology
• Crohn Disease/therapy
• Diagnosis, Differential
• Disease Management
• Gastrointestinal Tract/physiopathology
• Humans
• Medication Therapy Management
• Primary Health Care
• Remission Induction/methods
• Risk Factors
• Severity of Illness Index

• Harm Reduction
• Humans
• Nicotine/adverse effects
• Nicotine/pharmacokinetics
• Nicotine/pharmacology
• Nicotine/poisoning
• Tobacco Products/adverse effects
• Tobacco Products/toxicity
• Tobacco Use Cessation Devices/adverse effects

• Nicotine
• Osteoarthritis
• Smoking

GTS-21 (also known as DMBX-anabaseine), a selective α7 nicotinic acetylcholine receptor (α7nAChR) agonist, has previously been found to inhibit the inflammation associated with rheumatoid arthritis (RA). RA is an autoimmune disease, where an abnormal immune system plays a critical role in the occurrence and development of synovium inflammation and bone damage. However, prior to this study, the immunological mechanism by which GTS-21 protects against RA had not been elucidated. In the present study, the effects of GTS-21 on T helper 1 (Th1) cells, which have an important role in the inflammation associated with RA, were investigated. Peripheral blood mononuclear cells (PBMCs) and cluster of differentiation (CD)4⁺ T cells were separated from patients with RA, and the effects of GTS-21 on PBMCs stimulated with anti-CD3/-CD28 antibodies and CD4⁺ T cells were investigated in the context of Th1-cell differentiation. ELISA was used to analyze interferon (IFN)-γ expression and flow cytometric analysis was used to detect the percentage of IFN-γ⁺ CD3⁺CD8⁻ T cells. In addition, western blotting was employed to detect the levels of the T-box transcription factor TBX21, which is a Th1 cell-specific transcription factor. The present study showed that GTS-21 reduced IFN-γ production in PBMCs from patients with RA. Under conditions of Th1-cell differentiation, GTS-21 reduced the percentage of IFNγ⁺CD3⁺CD8⁻ T cells and IFN-γ production in the culture supernatant and also inhibited the expression of the Th1 cell-specific transcription factor TBX21. The effects of GTS-21 were blocked by the α7nAchR antagonist α-bungarotoxin, which increased the expression of IFN-γ and TBX21. This study demonstrated that GTS-21 is able to inhibit RA Th1-cell differentiation through activation of the α7nAchR.

• GTS-21
• TBX21
• Th1 cells
• rheumatoid arthritis
• α7nAchR

A search for novel and more efficient therapeutic modalities of inflammatory bowel disease (IBD) is one of the most important tasks of contemporary medicine. The anti-inflammatory action of nicotine in IBD might be therapeutic, but its toxicity due to off-target and nonreceptor effects limited its use and prompted a search for nontoxic nicotinergic drugs. We tested the hypothesis that SLURP-1 and -2—the physiological nicotinergic substances produced by the human intestinal epithelial cells (IEC) and immunocytes—can mimic the anti-inflammatory effects of nicotine. We used human CCL-241 enterocytes, CCL-248 colonocytes, CCRF-CEM T-cells, and U937 macrophages. SLURP-1 diminished the TLR9-dependent secretion of IL-8 by CCL-241, and IFNγ-induced upregulation of ICAM-1 in both IEC types. rSLURP-2 inhibited IL-1β-induced secretion of IL-6 and TLR4- and TLR9-dependent induction of CXCL10 and IL-8, respectively, in CCL-241. rSLURP-1 decreased production of TNFα by T-cells, downregulated IL-1β and IL-6 secretion by macrophages, and moderately upregulated IL-10 production by both types of immunocytes. SLURP-2 downregulated TNFα and IFNγR in T-cells and reduced IL-6 production by macrophages. Combining both SLURPs amplified their anti-inflammatory effects. Learning the pharmacology of SLURP-1 and -2 actions on enterocytes, colonocytes, T cells, and macrophages may help develop novel effective treatments of IBD.

Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation. Surveys document that most smokers would like to quit, and many have made repeated efforts to do so. However, conventional smoking cessation approaches require nicotine addicted smokers to abstain from tobacco and nicotine entirely. Many smokers are unable – or at least unwilling – to achieve this goal, and so they continue smoking in the face of impending adverse health consequences. In effect, the status quo in smoking cessation presents smokers with just two unpleasant alternatives: quit or suffer the harmful effects of continuing smoking. But, there is a third choice for smokers: tobacco harm reduction. It involves the use of alternative sources of nicotine, including modern smokeless tobacco products like snus and the electronic cigarette (E-cig), or even pharmaceutical nicotine products, as a replacement for smoking. E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking’s damaging effect, they also replace some of the rituals associated with smoking behaviour. Thus it is likely that smokers who switch to E-cigs will achieve large health gains. The focus of this article is on the health effects of using an E-cig, with consideration given to the acceptability, safety and effectiveness of this product as a long-term substitute for smoking.

• kyphosis
• hyperkyphosis
• kyphotic posture
• hunchback
• causes

• Autonomic nervous system
• acetylcholine
• alpha7 nicotinic receptor
• immune system
• immune-mediated diseases
• inflammation
• sepsis
• vagus nerve

• acetylcholine
• monocytes
• macrophages
• alpha7 nicotinic receptor
• tumor necrosis factor

• Adult
• Cell Line
• Female
• Ganglionic Stimulants/immunology
• Ganglionic Stimulants/pharmacology
• Humans
• Immunomodulation/drug effects
• Male
• Monocytes/drug effects
• Monocytes/immunology
• Nicotine/immunology
• Nicotine/pharmacology
• Receptors, Nicotinic/drug effects
• Receptors, Nicotinic/immunology
• Receptors, Nicotinic/metabolism
• Smoking/immunology
• Tumor Necrosis Factor-alpha/drug effects
• Tumor Necrosis Factor-alpha/immunology
• Up-Regulation
• alpha7 Nicotinic Acetylcholine Receptor

• R01 GM084125 NIGMS NIH HHS

Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell.

• barrett's esophagus
• smoking
• cigarettes
• gastroesophageal reflux
• gerd

• Colitis, Ulcerative/physiopathology
• Crohn Disease/microbiology
• Crohn Disease/physiopathology
• Culture Media
• Humans
• Mycobacterium avium subsp. paratuberculosis/drug effects
• Mycobacterium avium subsp. paratuberculosis/growth & development
• NAD/chemistry
• NAD/pharmacology
• Niacin/chemistry
• Niacin/pharmacology
• Niacinamide/chemistry
• Niacinamide/pharmacology
• Nicotiana/chemistry

In inflammatory disorders such as rheumatoid arthritis, cytokines and danger signals are sensed by the central nervous system, which adapts behavior and physiologic responses during systemic stress. The central nervous system can also signal the periphery to modulate inflammation through efferent hormonal and neuronal pathways. The brain and spinal cord are involved in this bidirectional interaction. A variety of neuronal pathways that modulate synovial inflammation have been implicated, including the sympathetic and the parasympathetic branches of the autonomic system. Another mechanism, the dorsal root reflex, involves antidromic signaling along somatic afferent fibers that influences joint inflammation by releasing neuropeptides and other neuromediators in the periphery. Some of the neurotransmitters and neuroreceptors involved have been identified in preclinical models and represent novel targets for the treatment of rheumatic diseases.

• colitis
• dorsal root ganglia
• hyperexcitability
• nicotinic receptor
• mice

A major site of initiation of inflammatory responses upon physical perturbation(s) and infection by invading organisms is the skin. Control of responses in this organ is, in part, modulated by the neuronal nicotinic acetylcholine receptor (nAChR) alpha7.

To further investigate the role of alpha7 in skin inflammatory responses, a local inflammatory response was induced by topical application of croton oil to the ear skin of wild-type (alpha7WT) and alpha7 knock-out (alpha7KO) mice. Cells infiltrating the inflamed tissue were characterized by flow cytometry and RNA analysis.

Six hours following croton oil application, analysis of infiltrating cells showed that the alpha7KO mice exhibited a significantly enhanced number of cells, and specifically, of Ly6G positive neutrophils. Macrophage and lymphocyte infiltration was equivalent in the alpha7KO and alpha7WT mice. RNA analysis showed that IL-1β and IL-6 were increased significantly in the infiltrating cells of the alpha7KO mouse, although TNF failed to reach significance. In contrast, resident cells of the skin exhibited no differences in these cytokines between genotypes. Both resident and infiltrating cell populations from alpha7KO mice did show elevated message levels for the adhesion protein ICAM1. Measurement of chemokines revealed enhanced expression of the skin-related CCL27 by resident cells in alpha7KO mice. Further, we demonstrate that the population of Ly6G⁺ neutrophils at the croton oil-inflamed skin site expresses low levels of CCR10, a receptor for CCL27 normally associated with lymphocytes.

nAChRalpha7 in the skin can impact on early local inflammatory responses mediated through a novel population of neutrophils that are Ly6G⁺CCR10^lo.

Background. Smoking has a detrimental effect in Crohn's disease (CD), but this may be due to factors in smoking other than nicotine. Given that transdermal nicotine benefits ulcerative colitis (UC), and there is a considerable overlap in the treatment of UC and CD, the possible beneficial effect of nicotine has been examined in patients with Crohn's colitis. Aims. To assess the efficacy and safety of nicotine enemas in active Crohn's colitis. Patients. Thirteen patients with active rectosigmoid CD; 3 patients were excluded because they received antibiotics. Methods. Subjects were given 6 mg nicotine enemas, each day for 4 weeks, in an open pilot study. At the beginning and end of the trial, a Crohn's disease activity index (CDAI) score was calculated, sigmoidoscopy was performed, and haematological inflammatory markers measured. Results. Mean CDAI decreased from 202 to 153—the score was reduced in 6 patients, unchanged in 3, and increased in one. Frequency of bowel movements decreased in 8 patients and the sigmoidoscopy grade was reduced in 7. Mean C-reactive protein decreased from 22.0 to 12.3 mg/L. There were no withdrawals due to adverse events. Conclusions. In this relatively small study of patients with active Crohn's colitis, 6 mg nicotine enemas appeared to be of clinical benefit in most patients. They were well tolerated and safe.

Human β-defensin-2 (HBD2) is an antimicrobial peptide implicated in the pathogenesis of inflammatory bowel disease (IBD). Low copy number and concomitant low mRNA expression of the HBD2 gene have been implicated in susceptibility to colonic Crohn's Disease (CD). We investigated the colonic distribution of HBD2 mRNA expression, and the contributions of genetic and environmental factors on HBD2 protein production.

We examined HBD2 mRNA expression at three colonic locations by microarray analysis of biopsies from 151 patients (53 CD, 67 ulcerative colitis [UC], 31 controls). We investigated environmental and genetic influences on HBD2 protein production using ex vivo cultured sigmoid colon biopsies from 69 patients (22 CD, 26 UC, 21 controls) stimulated with lipopolysaccharide (LPS) and/or nicotine for 24 hours. HBD2 and cytokines were measured in culture supernatants. Using DNA samples from these patients, regions in the HBD2 gene promoter were sequenced for NF-κB binding-sites and HBD2 gene copy number was determined. HBD2 mRNA expression was highest in inflamed (vs. uninflamed p = 0.0122) ascending colon in CD and in inflamed (vs. uninflamed p<0.0001) sigmoid colon in UC. HBD2 protein production was increased in inflamed UC biopsies (p = 0.0078). There was no difference in HBD2 protein production from unstimulated biopsies of CD, UC and controls. LPS-induced HBD2 production was significantly increased in CD (p = 0.0375) but not UC (p = 0.2017); this LPS-induced response was augmented by nicotine in UC (p = 0.0308) but not CD (p = 0.6872). Nicotine alone did not affect HBD2 production. HBD2 production correlated with IL8 production in UC (p<0.001) and with IL10 in CD (p<0.05). Variations in the HBD2 promoter and HBD2 gene copy number did not affect HBD2 production.

Colonic HBD2 was dysregulated at mRNA and protein level in IBD. Inflammatory status and stimulus but not germline variations influenced these changes.

• Alzheimer Disease/physiopathology
• Animals
• Brain/physiology
• Disease Models, Animal
• Gene Expression Regulation/physiology
• Humans
• Parkinson Disease/physiopathology
• Receptors, Nicotinic/chemistry
• Receptors, Nicotinic/physiology

• U01 NS059344 NINDS NIH HHS
• U01 NS059344-02 NINDS NIH HHS
• P01 HL072903 NHLBI NIH HHS
• R01 NS025296-17 NINDS NIH HHS
• U01 NS059344-01 NINDS NIH HHS
• P01-HL-72903 NHLBI NIH HHS
• R01 NS025296 NINDS NIH HHS
• R01 NS025296-19 NINDS NIH HHS
• U01-NS-59344 NINDS NIH HHS
• AG-17517 NIA NIH HHS
• NS-25296 NINDS NIH HHS
• U01 NS059344-03 NINDS NIH HHS
• R01 AG017517 NIA NIH HHS
• R01 NS025296-18 NINDS NIH HHS