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P279. Circulating cytokines profiles in children with inflammatory bowel disease under infliximab therapy

L. Kuznetsova1, S. Petrichuk1, A. Potapov2, E. Tsimbalova2, 1Scientific Center of Children's Health, Cytochemical laboratory, Moscow, Russian Federation, 2Scientific Center of Children's Health, Gastroenterology department, Moscow, Russian Federation

Background

Anti-cytokine therapy efficacy assessment is usually based on clinical, endoscopic and mostly non-specific laboratory criteria. Serum cytokines level measurement of IBD children treated with infliximab can be considered as a specific laboratory marker of anti-cytokine therapy effect.

Methods

We prospectively investigated circulating cytokines profiles of 70 IBD children. These patients were 44 children with Crohn's disease (CD) and 26 patients with ulcerative colitis (UC) at the age from 10 to 18 years, who were treated with infliximab for a long period. We measured IL-1 β, IL-2, IL-6, IL-8, IFN-γ, TNF-α, β, IL-5, IL-10, IL-4, IL-12p70 serum concentrations by FlowCytomix humanTh1/Th2 11plex kits (Bender MedSystems) with a help of flow cytometer Beckman Coulter FC500 (USA). Clinical effect of the therapy was assessed using pediatric Crohn's disease activity index (PCDIA) and pediatric ulcerative colitis activity index (PUCAI).

Results

According to the clinical effect, all patients were divided into 2 groups – children with sustained effect (Grp1) and patients with nonsustained effect (Grp0) of infliximab. 86% children from Grp1 and only 9% Grp0 patients had increased TNF-α baseline level (more than 10 pg/ml, normal rates were taken from Vector-Best company data, Russia). Mean cytokines baseline serum concentrations in Grp1and Grp0 are shown in Figure 1.

Circulating cytokines profiles of children from Grp1 were characterized by significantly high cytokines levels than those in the Grp0, excluding IL-1 β and TNF- β.

There were no statistically significant differences between CD's and UC's patients baseline cytokines concentrations. After the year of infliximab therapy we observed 50% patients from Grp1 and 14% Grp0 children with increased TNF-α serum concentration, mean values were 29.3 pg/ml and 6.0 pg/ml respectively (p < 0.001). Concentrations of other cytokines serum were also higher in Grp1.

Figure 1.

Table 1. Cytokines concentration, pg/ml (P < 0.003)
 Cytokines concentration (pg/ml), mean±SE
 Group 0Group 1
IFN-γ11.1±5.1146.3±40.3
IL-259.2±9.5349.4±46.5
IL-1011.6±4.9134.7±51.7
IL-898.5±34.8401.0±100.3
IL-64.6±1.255.2±20.4
IL-441.2±19.81546.5±467.3
IL-547.2±18.4231.5±98.4
TNF-α2.3±1.0107.5±40.3

Conclusion

Base circulating cytokines profiles evaluation in children with IBD can be used as additional prognostic criteria of anti-cytokines therapy effect.