Anti-TNF Therapies Suppress Adipose Tissue Inflammation in Crohn’s Disease

Abstract

Anti-TNF biologics have been shown to markedly improve the quality of life for patients with Crohn’s disease (CD), yet one-third of patients fail to benefit from this treatment. Patients with CD develop a characteristic wrapping of visceral adipose tissue (VAT) in the inflamed intestinal area, termed creeping fat, and it is known that adipose tissue expansion influences the efficacy of anti-TNF drugs. We questioned whether anti-TNF therapies impact the creeping fat in CD, which might affect the outcome of the disease. Adipose tissue biopsies were obtained from a cohort of 14 patients with CD that received anti-TNF drugs and from 29 non-anti-TNF-treated patients (control group) matched by sex, age, and body mass index undergoing surgical interventions for symptomatic complications. We found that anti-TNF therapies restored adipose tissue morphology and suppressed immune cell infiltration in the creeping fat. Additionally, anti-TNF treatments appeared to markedly improve the pro-inflammatory phenotype of adipose-tissue macrophages and adipose-tissue-derived stem cells. Our study provides evidence that anti-TNF medications influence immune cells and progenitor cells in the creeping of patients with CD, suppressing inflammation. We propose that perilesional VAT should be considered when administering anti-TNF therapy in patients with CD.

Patients With Inflammatory Bowel Diseases and Higher Visceral Adipose Tissue Burden May Benefit From Higher Infliximab Concentrations to Achieve Remission

“…Moreover, there are accumulating clinical and experimental data that suggest that VAT is the metabolically active component of total adiposity and may have a role in the pathogenesis of IBD through the release of cytokines and adipokines (18,19). VAT may possibly be serving as a TNF sink where local anti-TNF levels may not be high enough to overcome the TNF (and other cytokine) production in V2, increasing the antigen burden (20,21). Further studies looking into how VAT may affect infliximab concentrations and clearance in V2 and intercompartmental clearance are warranted.…”

Impacto da Terapia Biológica Anti-Fator de Necrose Tumoral (Anti-TNF) na Sensibilidade à Insulina em Pacientes com Doença de Crohn: Uma Revisão Bibliográfica

“…Em relação ao uso da terapia biológica para o tratamento da doença de Crohn se recomenda o uso de Inflaximab, Adalimumab, Certolizumab, ambos com a ação anti fator de necrose tumoral (Toscano et al, 2022). O anti-IL12 -23 que atua como bloqueadores destas interleucinas e a integrina y4y7, que bloqueia a integrina no intestino.…”