KMID : 1188320110050010037
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Gut and Liver 2011 Volume.5 No. 1 p.37 ~ p.45
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Infliximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn¡¯ Disease
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Kato Kyoichi
Kashiwamura Shinichiro Hida Nobuyuki Ohda Yoshio Takeda Naohisa Kamikozuru Koji Iimuro Masaki Yokoyama Yoko Kikuyama Risa Miwa Hiroto Matsumoto Takayuki
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Abstract
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Background/Aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-? 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¡¾92.9 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-?1 (p<0.01), and ¡¯egulated on activation, normal T cell expressed and secreted¡¯U (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-? (p<0.04), IL-6 (p<0.03), interferon (IFN)-? (p<0.04), IFN-?-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage infl ammatory protein-1? (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-?)/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 naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance.
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KEYWORD
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Crohn¡¯ disease, Infl iximab, Transforming growth factor-?1, RANTES, Regulatory T-cell
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