Cytokine Network in Rectal Mucosa in Perianal Crohn’S Disease: Relations with Inflammatory Parameters and Need for Surgery
Cesare Ruffolo1, Marco Scarpa1, Diego Faggian2, Anna Pozza1, Filippo Navaglia2, Renata D'Incà4, Pravera Hoxha2, Giovanna Romanato3, Lino Polese1, Giacomo C. Sturniolo4, Mario Plebani2, Davide F. D'Amico1, Imerio Angriman*1
1Clinica Chirurgica 1^, University of Padova, Padova, Italy; 2Medicina di Laboratorio, University of Padua, Padua, Italy; 3CNR-Institute of Neurosciences - Aging Section, Padua, Italy; 4Gastroenterologia, University of Padua, Padua, Italy
Background: Nowadays anti-TNF-alpha antibodies are often used for the therapy of perianal Crohn’s disease. Nevertheless this treatment is effective only in a part of these patients and recent studies suggested an important role for other cytokines, such as IL-6, IL-1beta, IL-12 and TGF-beta1 in chronic bowel inflammation. Aim: The aim of this study was to assess the cytokine profile in the rectal mucosa of patients affected by perianal Crohn’s diseases and to understand its relations with the systemic cytokine profile, the systemic inflammatory parameters and the need for surgery. Patients and
Methods: Seventeen patients affected by perianal Crohn’s disease, 7 affected by Crohn’s disease without perianal involvement and 17 healthy controls were enrolled in this study and underwent blood sampling and endoscopy. During endoscopy two rectal mucosal samples were taken and expression of TNF-alpha, IL-6,IL-1beta, IL-12 e TGF-beta1 was quantified with ELISA. Local cytokine levels were then compared and correlated to diagnosis, therapy, phenotype (fistulizing and stenosing) and disease activity parameters.
Results: In the group with perianal Crohn’s disease rectal mucosal IL-1beta, IL-6 and serum IL-6 and TNF-alpha were higher than in patients with small bowel Crohn’s disease and healthy controls. IL-12 and TGF-beta1 mucosal levels did not show any differences among the three groups. Mucosal IL-6 significantly correlated with PDAI and mucosal TNF-alpha and IL-1beta. Mucosal TNF-alpha and IL-1beta showed a direct correlation with the histological grade of disease activity.
Conclusions: The cytokines network analysis in perianal CD shows the important involvement of IL-1beta, IL-6 and TNF-alpha produced by macrophage and dendritic cells. These results seem to suggest that IL-6 and IL-1beta might be alternative targets of an immunomodulatory therapy in case of anti-TNF-alpha failure.
