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Complement activation in plasma before and after infliximab treatment in Crohn disease
E Zimmermann-Nielsen1, J Agnholt, O Thorlacius-Ussing
1Dept. of Surgery K, Hospital of Funen, Svendborg Sygehus, Svendborg, Denmark. erzn.shf-post1@fyns-amt.dk
Insights
Infliximab treatment for Crohn disease reduced immune activation markers, including complement system (C) pathways. This suggests Infliximab down-regulates inflammation in Crohn disease patients.
Area of Science:
- Immunology
- Gastroenterology
Background:
- Crohn disease involves intestinal inflammation, often linked to tumor necrosis factor alpha (TNF-alpha).
- The complement system (C) may also contribute to sustained inflammation in Crohn disease.
Purpose of the Study:
- To investigate the role of the complement system in Crohn disease.
- To assess the impact of Infliximab treatment on complement activation in Crohn disease patients.
Main Methods:
- Collected plasma from 26 Crohn disease patients with fistulizing ano-rectal disease before and after three Infliximab infusions.
- Measured complement C3-activation capacities (C3-AC) and other inflammatory markers.
Main Results:
- Before treatment, C3-AC levels in Crohn disease patients were similar to healthy controls.
- Infliximab treatment significantly decreased classical complement pathway C3-AC, mannan-binding lectin C4-AC, leucocyte count, C-reactive protein, and Crohn Disease Activity Index.
- These changes were observed 8 weeks after the first Infliximab infusion.
Conclusions:
- All three complement pathways were within normal ranges before Infliximab treatment.
- The reduction in classical pathway C3-AC post-Infliximab indicates a general down-regulation of immune activation in Crohn disease.
Background:
Crohn disease is characterized by up-regulated intestinal inflammation mainly caused by increased tumour necrosis factor alpha (TNF-alpha) levels. However, the complement system (C) may also have a role in maintaining inflammation.
Methods:
Plasma from 26 patients with Crohn disease complicated by fistulizing ano-rectal disease was collected before and after three Infliximab infusions (5 mg kg(-1)).
Results:
Before treatment, the C3-activation capacities (C3-AC) in plasma from patients with Crohn disease were comparable with values obtained from healthy controls. The classical C pathway-mediated C3-AC, mannan-binding lectin C4-AC, leucocyte count, C-reactive protein concentration and Crohn Disease Activity Index decreased significantly 8 weeks after the first infusion of Infliximab (P < 0.04, Wilcoxon test).
Conclusions:
Before treatment, all three C pathways were within the normal range in plasma from patients with Crohn disease; the decrease observed in the classical pathway-mediated C3-AC after treatment with Infliximab reflects a general down-regulation in immune activation.
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