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P084. Effect of infliximab on monocyte subtypes in blood of patients with chronic inflammatory bowel disease

S. Slevin1, C. Dennedy1, M. Griffin1, L. Egan2, 1National University of Ireland, Galway, REMEDI, Galway, Ireland, 2National University of Ireland, Galway, Department of Pharmacology and Therapeutics, Galway, Ireland

Background

Monocytes are multi-functional myeloid cells with roles in homeostasis, tissue repair and they also play a dominant part in the link between the innate and adaptive immune system. Monocytes are believed to be involved in the pathogenesis of chronic inflammatory disorders such as inflammatory bowel disease (IBD) and drugs active against IBD may exert their benefits at least in part through actions on monocytes. A new monocyte classification has been proposed that uses CD14 and CD16 expression as determined by flow cytometry to define three functionally distinct classes: CD14++ CD16 (classical), CD14++ CD16+ (intermediate) and CD14+ CD16++ (non-classical). To date, little is known about these monocyte subsets in IBD patients. This study was aimed at applying this monocyte classification system to Crohn's disease patients and determining any effect of the anti-TNFalpha monoclonal antibody infliximab on them.

Methods

Blood was taken pre and immediately post infusion with infliximab, and was processed to extract mononuclear cells. Monocytes were labelled using CD14 and CD16 antibodies and analysed using flow cytometry.

Results

See the table.

A paired sample t-test was carried out to show if the difference in total monocyte numbers pre and post infusion of infliximab was significant. Results show that Crohn's disease patients on treatment with infliximab have lower total monocyte counts than do healthy controls. Immediately after an infusion of infliximab, the numbers of classical and intermediate monocytes, but not non-classical monocytes were significantly lowered compared to before the infusion.

 Number of total peripherally circulating monocytes (monocytes/mL)
 Healthy controls (n = 16)Pre-infusion (n = 7)Post-infusion (n = 7)P-value
All monocytes150,253.5041,257.1418,514.29<0.01
Classical monocytes104,837.0825,177.698,206.950.01
Intermediate monocytes33,986.6912,321.665,891.41<0.01
Non-classical monocytes11,429.733,340.642,921.55NS
(Control n = 16, pre and post infusion n = 7) P-value is pre- versus post-infusion. NS = not significant.

Conclusion

These results show that monocyte numbers are different between healthy controls and Crohn's disease patients on treatment with infliximab, and that the drug selectively lowers certain monocyte sub-populations. These findings are being expanded to include patients not infliximab treatment, and patients with ulcerative colitis. In conclusion, monocyte sub-population analysis using flow cytometry may provide insights into disease pathogenesis and treatment responses.