INFLAMMATORY MEDIATORS AND IMMUNE RESPONSE IN CROHN'S DISEASE: MECHANISMS, IMPACT, AND THERAPEUTIC PERSPECTIVES

• DOI: https://doi.org/10.22533/at.ed.1595122524021

• Palavras-chave: Crohn's disease, Chronic inflammation, Gastrointestinal tract, Immune system

• Keywords: Crohn's disease, Chronic inflammation, Gastrointestinal tract, Immune system

• Abstract:

  Crohn's disease is a chronic inflammation of the gastrointestinal tract resulting from the deregulated activation of the immune system, leading to chronic transmural inflammation. CD4+ T cells, alongside macrophages and neutrophils, play a central role in the pathology and, after being activated by antigens from their own intestinal microbiota or food, release inflammatory cytokines (TNF-α, IL-6, IL-12, IL-23) that cause damage to the intestinal mucosa, favoring complications in this epithelium, such as ulcers, fistulas and stenosis. 
  This leads to the formation of an inflammatory cycle, consisting of both the summoning of more inflammatory cells due to the action of the cytokines released and other mechanisms, such as dysbiosis of the intestinal microbiota, which facilitates inadequate activation of the immune system and increases intestinal permeability. In addition, certain genetic factors, such as the NOD2, ATG16L1 and IL23R genes, are predisposing factors and contribute to disease recurrences by influencing the development of an exacerbated immune response, making clinical management more difficult. The complexity of the pathology is also related to the fact that its transmural involvement compromises all layers of the intestinal wall, and even in apparent remission, subclinical inflammation can remain. Considering this situation, continuous monitoring with biomarkers such as fecal calprotectin makes it possible to detect inflammation before it becomes symptomatic. Treatment consists of immunomodulators and biological therapies such as anti-TNF (infliximab and adalimumab) and IL-12/23 inhibitors, which act by reducing inflammation and contribute to maintaining remission. New approaches, such as JAK inhibitors, are being studied for patients refractory to the usual therapies. It should be noted that the progression of the disease is also influenced by environmental factors, including diet, which directly affects the intestinal microbiota, smoking and stress, both factors related to the effectiveness of treatment and control of recurrences. It is therefore understood that, despite numerous therapeutic advances, Crohn's disease remains a pathology in which a multidisciplinary approach is essential to improve quality of life and reduce the recurrence of inflammation.