Infliximab therapy impacts the peripheral immune system of immunomodulator and corticosteroid naïve patients with Crohn's disease

Gut Liver. 2011 Mar;5(1):37-45. doi: 10.5009/gnl.2011.5.1.37. Epub 2011 Mar 16.


Background/aims: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-α has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles 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 first 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 significantly 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-β1 (p<0.01), and 'regulated on activation, normal T cell expressed and secreted' (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-α (p<0.04), IL-6 (p<0.03), interferon (IFN)-γ (p<0.04), IFN-γ-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage inflammatory protein-1β (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-γ)/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.

Keywords: Crohn's disease; Infliximab; RANTES; Regulatory T-cell; Transforming growth factor-β1.