Gut and Liver 2011; 5(1): 37-45 https://doi.org/10.5009/gnl.2011.5.1.37 Infliximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn' Disease
Author Information
Kyoichi Kato*, Ken Fukunaga*, Koji Kamikozuru*, Shinichiro Kashiwamura, Nobuyuki Hida*, Yoshio Ohda*, Naohisa Takeda*, Koji Yoshida*, Masaki Iimuro*, Yoko Yokoyama*, Risa Kikuyama*,‡, Hiroto Miwa§, and Takayuki Matsumoto*
*Division of Lower Gastroenterology, Department of Internal Medicine, Department of Biology, Hyogo College of Medicine, Hyogo, Department of Gastroenterology, Faculty of Medicine, Mie University, Mie, and §Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

Ken Fukunaga
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

Abstract
Background/Aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-Ձ has effi cacy in treating Crohn' disease (CD). However, knowledge of the potential effects of IFX on patients'immune profi les is lacking. The purpose of this study was to reveal the immunological effects of IFX. Methods: Twenty-two patients with a CD activity index (CDAI) of 194.2±92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their fi rst IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/ CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. Results: CDAI signifi cantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-Ղ1 (p<0.01), and 'egulated on activation, normal T cell expressed and secreted'Ù (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-Ձ (p<0.04), IL-6 (p<0.03), interferon (IFN)-Ճ (p<0.04), IFN-Ճ-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage infl ammatory protein-1Ղ (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-Ճ)/Th2 (IL-4) ratio (p<0.03). Conclusions: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naïve Th0 lymphocytes to Treg. This knowledge should have clinical relevance. (Gut Liver 2011;5:37-45)
Keywords: Crohn' disease; Infl iximab; Transforming growth factor-Ղ1; RANTES; Regulatory T-cell
Abstract
Background/Aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-Ձ has effi cacy in treating Crohn' disease (CD). However, knowledge of the potential effects of IFX on patients'immune profi les is lacking. The purpose of this study was to reveal the immunological effects of IFX. Methods: Twenty-two patients with a CD activity index (CDAI) of 194.2±92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their fi rst IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/ CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. Results: CDAI signifi cantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-Ղ1 (p<0.01), and 'egulated on activation, normal T cell expressed and secreted'Ù (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-Ձ (p<0.04), IL-6 (p<0.03), interferon (IFN)-Ճ (p<0.04), IFN-Ճ-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage infl ammatory protein-1Ղ (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-Ճ)/Th2 (IL-4) ratio (p<0.03). Conclusions: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naïve Th0 lymphocytes to Treg. This knowledge should have clinical relevance. (Gut Liver 2011;5:37-45)
Keywords: Crohn' disease; Infl iximab; Transforming growth factor-Ղ1; RANTES; Regulatory T-cell
Search for
Services
Archives