PMID- 28796316
OWN - NLM
STAT- MEDLINE
DCOM- 20181011
LR  - 20220129
IS  - 1365-2362 (Electronic)
IS  - 0014-2972 (Linking)
VI  - 47
IP  - 10
DP  - 2017 Oct
TI  - Effects of tocilizumab on neutrophil function and kinetics.
PG  - 736-745
LID - 10.1111/eci.12799 [doi]
AB  - BACKGROUND: Decreases 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 METHODS: Eighteen 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. RESULTS: Mean 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. CONCLUSIONS: We have demonstrated for the first time in humans that 
      IL-6R blockade affects neutrophil trafficking to the bone marrow without 
      influencing neutrophil functional capacity.
CI  - (c) 2017 Stichting European Society for Clinical Investigation Journal Foundation.
FAU - Lok, Laurence S C
AU  - Lok LSC
AUID- ORCID: 0000-0002-9364-4213
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
FAU - Farahi, Neda
AU  - Farahi N
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
FAU - Juss, Jatinder K
AU  - Juss JK
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
FAU - Loutsios, Chrystalla
AU  - Loutsios C
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
FAU - Solanki, Chandra K
AU  - Solanki CK
AD  - Department of Nuclear Medicine, Cambridge University Hospitals NHS Foundation 
      Trust, Cambridge, UK.
FAU - Peters, Adrien M
AU  - Peters AM
AUID- ORCID: 0000-0002-4623-3614
AD  - Division of Clinical and Laboratory Investigation, Brighton and Sussex Medical 
      School, Brighton, UK.
FAU - Donaldson, Francis
AU  - Donaldson F
AD  - Roche Products Ltd., Welwyn Garden City, UK.
FAU - Porter-Brown, Benjamin
AU  - Porter-Brown B
AD  - Roche Products Ltd., Welwyn Garden City, UK.
FAU - Chilvers, Edwin R
AU  - Chilvers ER
AD  - Department of Medicine, University of Cambridge, Cambridge, UK.
LA  - eng
GR  - MR/J00345X/1/MRC_/Medical Research Council/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170831
PL  - England
TA  - Eur J Clin Invest
JT  - European journal of clinical investigation
JID - 0245331
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - I031V2H011 (tocilizumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/pharmacokinetics
MH  - Apoptosis/*drug effects
MH  - Cell Movement/*drug effects
MH  - Healthy Volunteers
MH  - Humans
MH  - Infusions, Intravenous
MH  - Kinetics
MH  - Male
MH  - Middle Aged
MH  - Neutrophils/cytology/*drug effects/physiology
MH  - Reference Values
MH  - Sensitivity and Specificity
MH  - Single-Blind Method
MH  - Young Adult
OTO - NOTNLM
OT  - Interleukin-6
OT  - neutrophil
OT  - tocilizumab
OT  - trafficking
EDAT- 2017/08/11 06:00
MHDA- 2018/10/12 06:00
CRDT- 2017/08/11 06:00
PHST- 2017/03/11 00:00 [received]
PHST- 2017/08/06 00:00 [accepted]
PHST- 2017/08/11 06:00 [pubmed]
PHST- 2018/10/12 06:00 [medline]
PHST- 2017/08/11 06:00 [entrez]
AID - 10.1111/eci.12799 [doi]
PST - ppublish
SO  - Eur J Clin Invest. 2017 Oct;47(10):736-745. doi: 10.1111/eci.12799. Epub 2017 Aug 
      31.