Background: In inflamed tissues of patients with inflammatory bowel disease (IBD), many immune and non-immune cells produce a vast array of cytokines, which contribute to expand and maintain the pathologic process. Key Message: Interleukin (IL)-12 and IL-23, 2 heterodimeric cytokines sharing the common p40 subunit, are over-produced in IBD and supposed to play a major role in promoting and/or sustaining the pro-inflammatory cytokine response in these disorders. IL-12 targets mostly T cells and innate lymphoid cells and through activation of Stat4 promotes T helper (Th)1 cell polarization, interferon-γ and IL-21 production, while IL-23 activates Stat3 thus amplifying Th17 cell programs. These observations together with the demonstration that IL-12 and IL-23 drive pathogenic responses in animal models of colitis have paved the way for the development of IL-12p40 blockers. Two monoclonal antibodies (ustekinumab and briakinumab) targeting p40 have been tested in Crohn's disease (CD) patients. Blockade of IL-12p40 is beneficial in CD patients resistant to tumor necrosis factor (TNF) antagonists and promotes resolution of psoriatic lesions that develop in IBD patients following anti-TNF therapy. Conclusions: The available human data support the pathogenic role of IL-12/IL-23 in IBD and suggest that IL-12p40 blockers could help manage some subsets of IBD patients.
Marafini, I., Angelucci, E., Pallone, F., & Monteleone, G. (2015). The IL-12/23/STAT Axis as a Therapeutic Target in Inflammatory Bowel Disease: Mechanisms and Evidence in Man. DIGESTIVE DISEASES, 33(1), 113-119 [10.1159/000437106].
|Tipologia:||Articolo su rivista|
|Citazione:||Marafini, I., Angelucci, E., Pallone, F., & Monteleone, G. (2015). The IL-12/23/STAT Axis as a Therapeutic Target in Inflammatory Bowel Disease: Mechanisms and Evidence in Man. DIGESTIVE DISEASES, 33(1), 113-119 [10.1159/000437106].|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Revisione (peer review):||Esperti anonimi|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1159/000437106|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2015|
|Titolo:||The IL-12/23/STAT Axis as a Therapeutic Target in Inflammatory Bowel Disease: Mechanisms and Evidence in Man|
|Autori:||Marafini, I; Angelucci, E; Pallone, F; Monteleone, G|
|Appare nelle tipologie:||01 - Articolo su rivista|