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Rheumatology Advance Access published online on November 23, 2008
Rheumatology, doi:10.1093/rheumatology/ken412
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Lactoferrin is a survival factor for neutrophils in rheumatoid synovial fluid

S. H. Wong1, N. Francis1, H. Chahal1, K. Raza1, M. Salmon1, D. Scheel-Toellner1 and J. M. Lord1

1Rheumatology Research Group, MRC Centre for Immune Regulation, Institute of Biomedical Research, Birmingham University, Birmingham, UK

Correspondence to: J. M. Lord, MRC Centre for Immune Regulation, Institute of Biomedical Research, Birmingham University, Birmingham B15 2TT, UK. E-mail: J.M.Lord{at}bham.ac.uk


  Abstract

Objectives. Lactoferrin is an iron-binding protein that is released from activated neutrophils at sites of inflammation and has anti-microbial as well as anti-inflammatory properties. This study set out to determine whether lactoferrin can delay neutrophil apoptosis and could act as a survival factor for neutrophils in SF.

Methods. Human peripheral blood and SF neutrophils were incubated with iron-free lactoferrin and apoptosis determined after 9 h. SF from patients with RA was added to isolated neutrophils, with or without immunodepletion of lactoferrin, and effects on neutrophil apoptosis determined. Levels of lactoferrin in SF were assessed and related to disease duration and markers of disease activity.

Results. Iron-free lactoferrin significantly delayed apoptosis of peripheral blood neutrophils, in a concentration-dependent manner after 9 h in culture (P < 0.04). Lactoferrin could also delay apoptosis of neutrophils isolated from SF of patients with RA. SF from patients with established RA delayed apoptosis of peripheral blood neutrophils and this effect was significantly reduced by depletion of lactoferrin (P < 0.03). Lactoferrin levels in SF from patients with established RA did not correlate with disease severity, but did correlate with markers of inflammation (CRP) and with the presence of RF. SF from patients with arthritis of <12 weeks duration did not contain significant levels of lactoferrin.

Conclusion. Lactoferrin contributes to extended neutrophil survival in the rheumatoid joint in the established phase of RA but not in very early arthritis.

KEY WORDS: Lactoferrin, Neutrophil, Apoptosis, Rheumatoid arthritis

S. H. Wong and N. Francis equally contributed to this work.

Submitted 15 April 2008; revised version accepted 23 September 2008.
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