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Biomedical subjects

A Klava

Publications and source records attributed to A Klava.

5 recordsLinked to original sources
PubMed1997

Interleukin-10. A role in the development of postoperative immunosuppression.

BACKGROUND: The cause of diminished monocyte major histocompatibility complex class II antigen expression after surgery or trauma is unclear. Interleukin-10 (IL-10) 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 +/- 0.8 pg/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.

Gene Expression↗
PubMed1997

Monocyte activation after open and laparoscopic surgery.

BACKGROUND: The level of expression of major histocompatibility complex class II antigens, human leucocyte antigen (HLA)-DR, on monocytes correlates with the development of sepsis after surgery or trauma. Normally interferon (IFN) gamma can increase monocyte HLA-DR expression and thus may be a potential biological prophylactic antisepsis agent in patients suffering from accidental or surgical trauma. The purpose of this study was to determine the capacity of monocytes to respond to IFN-gamma after conventional open surgery and laparoscopic surgery of similar magnitude. METHODS: A whole blood flow cytometric assay was used to measure monocyte HLA-DR antigen expression before and after monocyte activation with either IFN-gamma or bacterial lipopolysaccharide (LPS). Blood was obtained before operation and on postoperative day 1 from 43 patients undergoing conventional open surgery and from 15 undergoing laparoscopic surgery of similar magnitude. RESULTS: Whole blood monocyte HLA-DR expression fell significantly after both conventional open and laparoscopic surgery. IFN-gamma caused monocyte HLA-DR expression to rise by a median (interquartile range) of 43 (26-60) per cent and 63 (10-124) per cent before operation in the open and laparoscopic groups respectively. However, after operation the corresponding values were 20 (6-41) per cent and 26 (9-74) per cent (P < 0.003 in all cases). Identical findings but of greater magnitude were observed with LPS stimulation before and after operation in the two surgical groups. CONCLUSION: Monocyte HLA-DR expression is diminished by surgical operations and is relatively refractory to further stimulation by IFN-gamma or LPS after surgery. Laparoscopic surgery is as suppressive as conventional surgery in this regard. The resistance of postoperative monocytes to further activation by IFN-gamma suggests that this agent may be ineffective as a biological response modifier after major surgery or trauma.

Adult↗
PubMed1997

Enhanced polymorphonuclear leucocyte adhesion after surgical injury.

OBJECTIVE: To evaluate the relationship between the expression of the neutrophil adhesion receptor CD11b, functional neutrophil adhesion, and clinical outcomes in patients undergoing major surgical resections. DESIGN: Laboratory study. SETTING: University hospital, United Kingdom. SUBJECTS: 25 patients undergoing surgical resections for malignant disease. INTERVENTIONS: Blood obtained preoperatively and on postoperative days 1, 3, and 6. Neutrophils were assayed for CD11b expression in whole blood and following isolation using flow cytometry, and adhesion was measured using a chromogenic, gelatin-dependent adhesion assay, with and without stimulation by FMLP. Postoperative outcomes were classified as uncomplicated (n = 20) or sepsis according to ACCP/SCCM definitions (n = 5). RESULTS: Whole blood neutrophil CD11b expression was significantly increased on the first postoperative day and in all patients was significantly higher in the sepsis group (p < 0.001, ANOVA). There was a significant increase in CD11b expression above preoperative concentrations after separation and stimulation with FMLP only in the sepsis group, 3 and 6 days postoperatively (p < 0.01, paired t-test). Functional neutrophil adhesion was significantly higher in the sepsis compared with the uncomplicated group at all time points postoperatively (p < 0.001, two way ANOVA). CONCLUSION: Major operations are accompanied by upregulation of baseline CD11b expression mirrored by changes in neutrophil adhesion. Those patients who develop sepsis have greater degrees of CD11b expression and adhesion. These data present a potential pathophysiological role for neutrophils throughout the postoperative period in the development of sepsis and its sequelae after major operations.

Adult↗
PubMed1995

Manipulation of local and systemic host defence in the prevention of perioperative sepsis.

This review addresses some of the immunological issues surrounding the complex problem of perioperative sepsis. It identifies an immunological paradox between the relative immunosuppression of the immediate postoperative period and the relative immune activation of established sepsis, in addition to discussing current knowledge of the mechanisms surrounding these phenomena. Much remains unknown about perioperative immunoregulation; there are a number of potential mechanisms, however, whereby local and systemic immune defences can be modified or enhanced. Provided patients at risk can be identified, such manipulations may find application in preventing infection and sepsis after surgery.

Humans↗