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A Role in the Development of Postoperative Immunosuppression

Andrew Klava, MB; Alistair C. J. Windsor; Susan M. Farmery, PhD; Linda F. Woodhouse; John V. Reynolds, MCh; Carol W. Ramsden; Arthur W. Boylston, MD; Pierre J. Guillou, MD

Arch Surg. 1997;132(4):425-429.

Abstract
Background
The cause of diminished monocyte major histocompatibility complex class II antigen expression after surgery or trauma is unclear. Interleukin-10 (IL-1 0) regulates inflammatory cytokine production and major histocompatibility complex class II (HLA-DR) expression in vitro.

Objectives
To quantify in vivo IL-10 messenger RNA (mRNA) and protein and monocyte HLA-DR expression after major surgery and to investigate the effects of IL-10 neutralizing blockade on monocyte HLA-DR expression in vitro.

Design
Inception cohort study of 48 surgical patients from preoperative status to postoperative day 7 and 9 healthy volunteers (controls).

Setting
Large teaching hospital, Northern England.

Patients
Monocyte HLA-DR and cytokine mRNA expression was determined in 32 of 48 consecutive patients undergoing elective major resectional surgery. Mononuclear cells for in vitro studies and serum samples for IL-10 measurement were obtained from the remaining 16 patients.

Main Outcome Measures
Monocyte HLA-DR expression determined by flow cytometry, IL-10, and tumor necrosis factor mRNA in peripheral blood mononuclear cells assayed by multiplex reverse transcriptase polymerase chain reaction, and serum IL-10 determined by enzyme-linked immunosorbent assay.

Results
Monocyte HLA-DR expression (in mean channel fluorescence units [MCF]) was significantly reduced 24 hours after surgery (MCF [±SEM], 32.6±2.3 vs 16.3±1.2; P<.001) and remained low during the first postoperative week. A relative increase in IL-10 to G3PDH mRNA ratio (mean [±SEM],0.95±0.08 vs 0.59±0.06; P<.01) and serum IL-10 (mean [±SEM], 18.1±4.1 vs 5.4±0.8pg/mL; P<.01) was noted on the first postoperative day. A significant correlation existed between HLA-DR antigen expression and the presence of IL-10 mRNA transcript on the first postoperative day (P<.01). Lipopolysaccharide-induced up-regulation of monocyte HLA-DR expression was significantly impaired on the first postoperative day (mean [±SEM],151%±24.4% vs 60%±10.1%; P<.01), but this was partially reversed by IL-10 neutralizing antibody (mean [±SEM], 60%±10.1% vs 115%±11.6%; P<.01).

Conclusions
Interleukin-10 gene expression correlates with the fall in monocyte HLA-DR antigen expression in patients undergoing major abdominal surgery and may account for the immunosuppression associated with surgical injury.

Arch Surg. 1997;132:425-429

Author Affiliations
From the Academic Unit of Surgery (Messrs Klava, Windsor, Reynolds, Mss Woodhouse and Ramsden, and Drs Farmery and Guillou) and Department of Molecular Medicine (Dr Boylston), St James's University Hospital, Leeds, England.

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