title: Cytokine gene expression after total hip arthroplasty: surgical site versus circulating neutrophil response.
abstract: BACKGROUND
  After surgery, cytokines and chemokines are released at the surgical wound site, which can contribute to postoperative pain, local inflammation, and tissue repair. Multiple cell types are present that can release cytokines/chemokines at the wound site and, thus, the exact cellular source of these molecules is unclear. We sought to better understand the contribution of neutrophils to cytokine/chemokine gene expression at the surgical wound site during the initial postsurgery phase of total hip arthroplasty (THA).
  
  
  METHODS
  Hip drain fluid was collected at 24 h postsurgery from six patients undergoing standardized THA. In addition, venous blood was collected presurgery and 24 h postsurgery. Neutrophils were isolated, total RNA extracted, and a biotinylated cRNA probe generated. The probes were hybridized with a cDNA microarray containing approximately 100 oligonucleotide sequences representing various human cytokines/chemokines or receptor genes. Changes in gene expression seen in the microarray were verified by reverse transcription polymerase chain reaction.
  
  
  RESULTS
  In the microarray analysis of hip drain neutrophils, interleukin-1 receptor antagonist (IL1RN), interleukin-18 receptor 1 (IL18R1), macrophage migration inhibitory factor (MIF), and macrophage inflammatory protein 3alpha (CCL20) were upregulated, whereas interleukin-8 receptor beta (IL8RB/CXCR2) was consistently downregulated, compared with presurgery blood neutrophils. All of these changes were confirmed by reverse transcription polymerase chain reaction.
  
  
  CONCLUSIONS
  There is a distinct cytokine gene expression profile in neutrophils at the THA surgical wound site at 24 h postsurgery when compared with that found in presurgery circulating neutrophils. Understanding these changes may allow us to knowledgeably manipulate neutrophil activity to reduce postoperative pain and inflammation without impairing wound healing.
authors.affiliation: Department of Anesthesiology, Rush University Medical Center, Chicago, IL 60612, USA. asokumar@aol.com
authors.forename: Asokumar
authors.initials: A
authors.lastname: Buvanendran
authors.forename: Kendall
authors.initials: K
authors.lastname: Mitchell
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kroin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Iadarola
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019644:Arthroplasty, Replacement, Hip / Q000379:methods*; D054418:Chemokine CCL20 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053727:Interleukin-18 Receptor alpha Subunit / Q000378:metabolism; D053728:Interleukin-18 Receptor beta Subunit / Q000096:biosynthesis; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D016207:Cytokines; C508572:IL18R1 protein, human; C115629:IL18RAP protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053727:Interleukin-18 Receptor alpha Subunit; D053728:Interleukin-18 Receptor beta Subunit; D008263:Macrophage Migration-Inhibitory Factors
references.citation: Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):345-50
references.pmid: 11756671
references.citation: J Neurochem. 2007 Nov;103(4):1628-43
references.pmid: 17883394
references.citation: Front Biosci. 2004 Jan 01;9:283-9
references.pmid: 14766366
references.citation: Clin Ther. 2004 Dec;26(12):1960-75
references.pmid: 15823761
references.citation: Fertil Steril. 2006 May;85(5):1379-85
references.pmid: 16616746
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10614-9
references.pmid: 8855227
references.citation: J Immunol Methods. 1999 Dec 17;232(1-2):23-43
references.pmid: 10618507
references.citation: Am J Surg. 2004 May;187(5A):11S-16S
references.pmid: 15147986
references.citation: J Biol Chem. 1990 Jan 5;265(1):183-9
references.pmid: 2403554
references.citation: J Rheumatol. 2005 Dec;32(12):2291-8
references.pmid: 16331752
references.citation: Pain. 2003 Aug;104(3):471-480
references.pmid: 12927619
references.citation: J Pharmacol Exp Ther. 2004 Aug;310(2):710-7
references.pmid: 15075358
references.citation: J Leukoc Biol. 2001 Apr;69(4):513-21
references.pmid: 11310836
references.citation: J Urol. 2004 Oct;172(4 Pt 1):1504-9
references.pmid: 15371880
references.citation: Ann Rheum Dis. 2000 Nov;59 Suppl 1:i60-4
references.pmid: 11053091
references.citation: J Leukoc Biol. 2005 Dec;78(6):1215-22
references.pmid: 16204636
references.citation: J Immunol. 2001 Sep 1;167(5):2879-86
references.pmid: 11509635
references.citation: Anesthesiology. 2006 Mar;104(3):403-10
references.pmid: 16508385
references.citation: Cytokine. 2000 Jul;12(7):1156-9
references.pmid: 10880268
references.citation: Science. 1991 Sep 13;253(5025):1278-80
references.pmid: 1840701
references.citation: Nat Rev Immunol. 2003 Oct;3(10):791-800
references.pmid: 14502271
references.citation: J Exp Med. 1999 Nov 15;190(10):1375-82
references.pmid: 10562313
references.citation: Am J Pathol. 1998 Dec;153(6):1849-60
references.pmid: 9846975
references.citation: Adv Exp Med Biol. 2003;521:22-39
references.pmid: 12617562
references.citation: Science. 1991 Sep 13;253(5025):1280-3
references.pmid: 1891716
references.citation: Anesth Analg. 2003 Aug;97(2):534-540
references.pmid: 12873949
references.citation: Fertil Steril. 2005 Apr;83(4):865-72
references.pmid: 15820792
references.citation: J Immunol. 1995 Sep 1;155(5):2587-94
references.pmid: 7650389
references.citation: Life Sci. 2007 Aug 2;81(8):673-82
references.pmid: 17692876
references.citation: Nature. 1988 Aug 25;334(6184):698-700
references.pmid: 3137474
references.citation: Biochem Biophys Res Commun. 2004 Nov 5;324(1):317-20
references.pmid: 15465020