• Eur. J. Clin. Invest. · Oct 2017

    Randomized Controlled Trial Comparative Study

    Effects of tocilizumab on neutrophil function and kinetics.

    • LokLaurence S CLSChttp://orcid.org/0000-0002-9364-4213Department of Medicine, University of Cambridge, Cambridge, UK., Neda Farahi, Jatinder K Juss, Chrystalla Loutsios, Chandra K Solanki, Adrien M Peters, Francis Donaldson, Benjamin Porter-Brown, and Edwin R Chilvers.
    • Department of Medicine, University of Cambridge, Cambridge, UK.
    • Eur. J. Clin. Invest. 2017 Oct 1; 47 (10): 736-745.

    BackgroundDecreases in circulating neutrophils (polymorphonuclear leucocytes, PMNs) have been reported in patients treated with the anti-interleukin-6 receptor (IL-6R) antibody tocilizumab (TCZ); the mechanism for this is unclear. We hypothesize that TCZ reduces circulating neutrophils by affecting margination and/or bone marrow trafficking without affecting neutrophil function or apoptosis.Materials And MethodsEighteen healthy subjects were randomized to single intravenous dose of TCZ 8 mg/kg (n = 12) or placebo (n = 6) on day 0. On day 4, each subject had autologous indium-111-labelled neutrophils re-injected, and their kinetics quantified with longitudinal profiling in a whole body gamma-counter. TCZ-treated subjects were divided into two groups according to the extent of reduction in neutrophil count.ResultsMean day 4 neutrophil counts, as % baseline, were 101·9%, 68·3% and 44·2% in the placebo, TCZ-PMN-'high' and TCZ-PMN-'low' groups, respectively (P < 0·001). Following TCZ, neutrophil function, activation and apoptosis ex vivo were all unaffected. In vivo, there were no differences in early blood recovery or margination to liver/spleen and bone marrow; however, later neutrophil re-distribution to bone marrow was markedly reduced in the TCZ-PMN-low group (peak pelvic count as % day 4 count on: day 5, 188% placebo vs. 127% TCZ-PMN-low, P < 0·001; day 10, 180% placebo vs. 132% TCZ-PMN-low, P < 0·01), with a trend towards higher liver/spleen neutrophil retention.ConclusionsWe have demonstrated for the first time in humans that IL-6R blockade affects neutrophil trafficking to the bone marrow without influencing neutrophil functional capacity.© 2017 Stichting European Society for Clinical Investigation Journal Foundation.

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