Cytokine gene expression after total hip arthroplasty: surgical site versus circulating neutrophil response.
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.
Buvanendran
Asokumar
A
Department of Anesthesiology, Rush University Medical Center, Chicago, IL 60612, USA. asokumar@aol.com
Mitchell
Kendall
K
Kroin
Jeffrey S
JS
Iadarola
Michael J
MJ
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*
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
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