Antibodies to tumor necrosis factor (TNF)-alpha have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-alpha in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10-30-fold higher levels of TNF-alpha mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-alpha, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-alpha-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-alpha in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-alpha-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-alpha gene had been inactivated by homologous recombination. Complementation of TNF-alpha function in TNF-/- mice by the expression of a mouse TNF-alpha transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-alpha in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-alpha for the treatment of patients with Crohn's disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/eji.1830270722 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effects of inflammatory bowel diseases on sexual function in women.
Ir J Med Sci
January 2025
Department of Urology, Başkent University Alanya Application and Research Center, Antalya, Türkiye.
Background: Inflammatory bowel disease (IBD) is a chronic disease that includes Crohn's disease and ulcerative colitis. Studies found that 40-60% of women diagnosed with IBD have sexual dysfunction (SD).
Aims: To determine SD and associated factors in women with IBD.
Telocytes in inflammatory bowel diseases: contributions to pathology and therapeutic potentials.
Front Cell Dev Biol
January 2025
Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, PA, United States.
Telocytes, a novel mesenchymal cell population, are characterized by their distinctive long and slender projections known as telopodes and have garnered significant interest since their formal introduction to the literature in 2010. These cells have been identified in various tissues, including the gastrointestinal (GI) tract, where they are suggested to play important roles in maintaining structural integrity, immune modulation, and barrier function. Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation and fibrosis.
View Article and Find Full Text PDFLaparoscopic intracorporeal anastomosis open anastomosis for ileostomy reversal in Crohn's disease: A single center retrospective study.
World J Gastrointest Surg
January 2025
Department of General Surgery, Chongqing General Hospital, Chongqing 401120, China.
Background: There is an increased maturation of laparoscopic intracorporeal anastomosis techniques. However, research on its application for small bowel stoma reversal in patients with Crohn's disease (CD) is limited. Therefore, in this study, we compared the perioperative outcomes between laparoscopic intracorporeal ileostomy reversal (LIIR) and open ileostomy reversal (OIR).
View Article and Find Full Text PDFDisseminated Chickenpox Following Live Varicella Vaccination in a Crohn's Disease Patient on Combination Immunosuppression.
Case Rep Gastrointest Med
January 2025
Department of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan, USA.
Novel therapeutics used in the treatment of inflammatory bowel disease pose an increased risk of viral reactivation in patients. We present a case of a patient with refractory Crohn's disease (CD) who developed primary varicella (chickenpox) of a vaccine-viral strain after receiving combination immunosuppression with high-dose corticosteroids, tumor necrosis factor inhibitor (TNFi), and a Janus kinase inhibitor (JAKi) in the hospital. While this patient recovered and did not experience long term adverse effects, her case provides an opportunity for improvement.
View Article and Find Full Text PDFNeutrophils: From Inflammatory Bowel Disease to Colitis-Associated Colorectal Cancer.
J Inflamm Res
January 2025
Cancer Center, Daping Hospital, Army Medical University, Chongqing, People's Republic of China.
Inflammatory bowel disease (IBD) is a non-specific inflammatory disease of digestive tract, primarily manifesting as ulcerative colitis (UC) and Crohn's disease (CD). The precise etiology of IBD remains elusive. The interplay of genetic factors, environmental influences, and intestinal microbiota contributes to the establishment of an uncontrolled immune environment within the intestine, which can progressively lead to atypical hyperplasia and ultimately to malignancy over a long period.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!