Effects of IL-6 and IL-6 blockade on neutrophil function in vitro and in vivo

Rheumatology (United Kingdom)

Volumn 53, Issue 7, 2014, Pages 1321-1331

  Wright, Helen L ^a   Cross, Andrew L ^b   Edwards, Steven W ^a   Moots, Robert J ^b  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b UNIVERSITY HOSPITAL AINTREE   (United Kingdom)

Author keywords

IL 6; Neutropenia; Neutrophil; Rheumatoid arthritis; Tocilizumab

Indexed keywords

CD11B ANTIGEN; CD16 ANTIGEN; CD18 ANTIGEN; CD32 ANTIGEN; CD63 ANTIGEN; CD64 ANTIGEN; CELL SURFACE PROTEIN; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; INTERLEUKIN 8; L SELECTIN; OXIDOREDUCTASE; STAT3 PROTEIN; TOCILIZUMAB;

APOPTOSIS; ARTICLE; BACTERICIDAL ACTIVITY; CELL DEATH; CELL MIGRATION; CONTROLLED STUDY; DISEASE ACTIVITY; ENZYME ACTIVITY; HOST RESISTANCE; HUMAN; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; INTRACELLULAR SIGNALING; LEUKOCYTE FUNCTION; NEUTROPHIL; NEUTROPHIL CHEMOTAXIS; NEUTROPHIL COUNT; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RESPIRATORY BURST; UPREGULATION; WESTERN BLOTTING;

IL-6; NEUTROPENIA; NEUTROPHIL; RHEUMATOID ARTHRITIS; TOCILIZUMAB;

AGED; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; APOPTOSIS; ARTHRITIS, RHEUMATOID; CASE-CONTROL STUDIES; CELL MOVEMENT; CHEMOTAXIS; FEMALE; HUMANS; INTERLEUKIN-6; MALE; MIDDLE AGED; NEUTROPENIA; NEUTROPHILS; PHAGOCYTOSIS; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR;

EID: 84902959388     PISSN: 14620324     EISSN: 14620332     Source Type: Journal    
DOI: 10.1093/rheumatology/keu035     Document Type: Article

References (25)

1. Cronstein BN. Interleukin-6-a key mediator of systemicand local symptoms in rheumatoid arthritis. Bull NYU Hosp Jt Dis 2007; 65: S11-5.
2. Boss B, Neeck G. Correlation of il-6 with the classical humoral disease activity parameters ESR and CRP and with serum cortisol, reflecting the activity of the hpa axis in active rheumatoid arthritis. Z Rheumatol 2000; 59: II/62-4.
3. Jones SA, Richards PJ, Scheller J, Rose-John S. IL-6 transsignaling: the in vivo consequences. J Interferon Cytokine Res 2005; 25: 241-53.
4. Desgeorges A, Gabay C, Silacci P et al. Concentrations and origins of soluble interleukin 6 receptor-alpha in serum and synovial fluid. J Rheumatol 1997; 24: 1510-6.
5. Hurst SM, Wilkinson TS, McLoughlin RM et al. IL-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity 2001; 14: 705-14.
6. Biffl WL, Moore EE, Moore FA, Barnett CC Jr. Interleukin-6 suppression of neutrophil apoptosis is neutrophil concentration dependent. J Leukoc Biol 1995; 58: 582-4.
7. Afford SC, Pongracz J, Stockley RA, Crocker J, Burnett D. The induction by human interleukin-6 of apoptosis in the promonocytic cell line u937 and human neutrophils. J Biol Chem 1992; 267: 21612-6.
8. McNamee JP, Bellier PV, Kutzner BC, Wilkins RC. Effect of pro-inflammatory cytokines on spontaneous apoptosis in leukocyte sub-sets within a whole blood culture. Cytokine 2005; 31: 161-7.
9. Ottonello L, Frumento G, Arduino N et al. Differential regulation of spontaneous and immune complex-induced neutrophil apoptosis by proinflammatory cytokines. Role of oxidants, Bax and caspase-3. J Leukoc Biol 2002; 72: 125-32.
10. Emery P, Keystone E, Tony HP et al. Il-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 2008; 67: 1516-23.
11. Genovese MC, McKay JD, Nasonov EL et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to diseasemodifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 2008; 58: 2968-80.
12. Smolen JS, Beaulieu A, Rubbert-Roth A et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (option study): a doubleblind, placebo-controlled, randomised trial. Lancet 2008; 371: 987-97.
13. Maini RN, Taylor PC, Szechinski J et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in european patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum 2006; 54: 2817-29.
14. Jones G, Sebba A, Gu J et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the ambition study. Ann Rheum Dis 2010; 69: 88-96.
15. Nakamura I, Omata Y, Naito M, Ito K. Blockade of interleukin 6 signaling induces marked neutropenia in patients with rheumatoid arthritis. J Rheumatol 2009; 36: 459-60.
16. Suwa T, Hogg JC, English D, Van Eeden SF. Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow. Am J Physiol Heart Circ Physiol 2000; 279: H2954-60.
17. Suwa T, Hogg JC, Klut ME, Hards J, van Eeden SF. Interleukin-6 changes deformability of neutrophils and induces their sequestration in the lung. Am J Respir Crit Care Med 2001; 163: 970-6.
18. Walker F, Zhang HH, Matthews V et al. IL6/sIL6R complex contributes to emergency granulopoietic responses in G-CSF-and GM-CSF-deficient mice. Blood 2008; 111: 3978-85.
19. Wright HL, Bucknall RC, Moots RJ, Edwards SW. Analysis of synovial fluid and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy. Rheumatology 2011; 51: 451-9.
20. Wright HL, Chikura B, Bucknall RC, Moots RJ, Edwards SW. Changes in expression of membrane TNF, NF-kappaB activation and neutrophil apoptosis during active and resolved inflammation. Ann Rheum Dis 2011; 70: 537-43.
21. Frey N, Grange S, Woodworth T. Population pharmacokinetic analysis of tocilizumab in patients with rheumatoid arthritis. J Clin Pharmacol 2010; 50: 754-66.
22. Taylor EL, Rossi AG, Dransfield I, Hart SP. Analysis of neutrophil apoptosis. Methods Mol Biol 2007; 412: 177-200.
23. Hastings R, Ding T, Butt S et al. Neutropenia in patients receiving anti-tumor necrosis factor therapy. Arthritis Care Res 2010; 62: 764-9.
24. Ulich TR, del Castillo J, Guo KZ. In vivo hematologic effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBCs and WBCs. Blood 1989; 73: 108-10.
25. Hashizume M, Higuchi Y, Uchiyama Y, Mihara M. IL-6 plays an essential role in neutrophilia under inflammation. Cytokine 2011; 54: 92-9.