To study apoptosis in circulating CD14+/CD11b+ monocytes treated with the chimeric TNFa antibody infliximab in vitro and ex vivo.
The induction of apoptosis in circulating CD14+/ CD11b+ monocytes from peripheral blood was investigated in vitro in cells from 16 healthy subjects and ex vivo in cells from 6 patients with ankylosing spondylitis (AS) that were treated with infliximab. The monocytes from healthy donors were exposed in vitro to interferon-g (IFNg) and tumor necrosis factor - a (TNFa) in the presence or absence of subsequent infliximab. Induction of apoptosis was detected by staining with annexinV and propidium iodide (PI). Osteoclastogenic potential of monocytes was tested in vitro by growing cells on dentin wafers.
Treatment of monocytes from healthy donors with IFNg or TNFa caused a decrease in the number of CD14+/ CD11b+/ annexinV+ monocytes (p = 0.03) and of CD14+/CD11b+/PI+ monocytes after TNFa exposure (p=0.03). This effect which was reversed by infliximab. Correspondingly, 2 days after the first infliximab infusion in AS patients, the numbers of CD14+/ CD11b+/ annexinV+ and CD14+/ CD11b+/ PI+ monocytes increased, a change which was accompanied by a depletion of circulating monocytes. Based on their bone resorbing activity CD14+/ CD11b+ monocytes were further characterized as osteoclast precursor cells (OPC).
The findings of this study suggest that the anti - bone resorptive effects of infliximab are mediated by a rapid induction of apoptosis in OPC in patients with chronic inflammatory diseases.
Disclosure: M. Seitz, None; D. Aeberli, None; R. K. Kamgang, None; W. Hofstetter, None; D. Balani, None; P. M. Villiger, None.