The inflammatory cytokine response after autotransfusion of shed mediastinal blood

Background : The inflammatory response in patients undergoing cardiac surgery with cardiopulmonary bypass is well known and increased levels of inflammatory cytokines have been shown. High levels of cytokines have been reported in blood drained from the surgical field. The present study aimed to elucidate whether autotransfusion of shed mediastinal blood in itself causes increased cytokine levels in coronary artery bypass graft (CABG) patients.
Methods : A prospective, randomized controlled study was performed in 23 patients having elective uncomplicated CABG. Autotransfusion of shed mediastinal blood was done every hour for 18 h in group I. In group II, the shed mediastinal blood was accumulated for 4 h in the cardiotomy reservoir and then autotransfused every hour for the next 14 h. Plasma levels of tumour necrosis factor-α (TNFα) and interleukin (IL)-1α, IL-1β, IL-6 were measured. In vitro study of cytokine production was performed with or without stimulation (phytohaemagglutinin (PHA) and Escherichia coli (E. coli) lipopolysaccharide (LPS)).
Results : We found high levels of IL-6 in the shed mediastinal blood. However, autotransfusion of shed mediastinal blood did not lead to increased level of cytokines (TNFα, IL-1α, IL-1β and IL-6) in plasma in group I nor in group II. In vitro study showed activation of the leucocytes in the shed mediastinal blood with a significantly increased production of TNFα and IL-6 both in the stimulated and non-stimulated samples.
Conclusion : Shed mediastinal blood contains high levels of IL-6. However, autotransfusion of shed mediastinal does not cause measurable elevations in plasma levels of IL-6. In vitro study shows that autotransfusion activates leucocytes, which may enhance production of inflammatory cytokines.     

Cytokine Production and Bone Mineral Density at the Lumbar Spine and Femoral Neck in Premenopausal Women

Cytokines such as interleukin-1 (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) can influence both bone resorption and bone formation. The objective of this cross-sectional study was to examine the relationship between cytokine production by peripheral blood mononuclear cells (PBMC) and bone mineral density (BMD); the annual rate of change in BMD was examined. Subjects participating in a randomized clinical trial entitled the Women's Healthy Lifestyle Project in Allegheny County, Pennsylvania were used. They included 50 healthy premenopausal women, aged 45–52 years, who had regular menses within the past 3 months and were not on replacement estrogens. Dual-energy X-ray absorptiometry measurements at the AP lumbar spine and femoral neck were made at baseline and at the first annual exam using a Hologic QDR 2000 densitometer. Cytokine production of IL-1β, IL-6, and TNF-α by PBMC was measured at the annual exam. The median values for stimulated cytokine production by PBMC were 3.92 ng/ml, 31.3 ng/ml, and 1.05 ng/ml, for IL-1β, IL-6, and TNF-α, respectively. There were modest correlations between cytokine production and cross-sectional BMD, ranging from r =−0.30 to r =−0.13. Trends of greater spinal bone loss were observed in women with ``high' (≥75th percentile) cytokine production of stimulated IL-1β and IL-6 (IL-1β: ``high' =−1.56% ± 0.70 versus ``low' (<75th percentile) =−0.56% ± 0.35, P= 0.21). In contrast, greater annual gains in femoral neck BMD were observed in those with high cytokine production of IL-1β and IL-6 (IL-1β: high = 3.39% ± 1.16 versus low =−0.85 ± 0.58, P= 0.002). There was no association between stimulated TNF production and annual change in BMD. In this population of healthy premenopausal women, the relationship between cytokine production by PBMC and the rate of change in BMD was significantly different for the lumbar spine and femoral neck, possibly reflecting differences in the proportion of trabecular and cortical bone at these sites. Received: 5 February 1997 / Accepted: 11 May 1998     

Cytokine response in the postoperative period after surgical treatment of benign adnexal masses: comparison between laparoscopy and laparotomy

Background Cytokines are the main mediators of the inflammation and the response to trauma. The purpose of the present study was the comparative assessment in sera of patients with benign adnexal masses treated by laparoscopy or laparotomy of the following proinflammatory and anti-inflammatory cytokines: interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), and IL-10 in the early postoperative period. Methods A total of 40 patients with benign adnexal masses were studied; 25 of whom underwent laparoscopy and 15, laparotomy. Blood serum concentration of IL-1β, IL-6, IL-8, TNF-α, and IL-10 were measured by commercially available ELISA assays before and 4 h, 24 h, and 48 h after the operation. Results Concentrations of IL-6 were significantly increased in both groups at 4 h, 24 h, and 48 h after the surgery; levels of IL-10 showed a significant increase 4 h and 24 h after the operation; an increase in IL-1β levels was observed only after laparotomy; no significant variations were observed in serum levels of IL-8; the postoperative increase of IL-1β, IL-6, and IL-10 levels was more pronounced in patients undergoing laparotomy than in those treated laparoscopically; length of the surgical procedure, amount of CO₂ used, tumor diameter, age, and body mass index (BMI) of the patients did not influence the postoperative patterns of the studied cytokines. Conclusions Systemic cytokine response after operations for benign adnexal masses depends on the degree of the surgical trauma, and is less pronounced in patients undergoing laparoscopy.     

Elevated urinary cytokine levels in patients undergoing ileal neobladder replacement compared with sigmoid neobladder replacement

Objectives The objective of this study was to examine the urinary cytokine levels for assessment of inflammatory conditions in patients with orthotopic neobladder. Materials and methods Urinary levels of IL-1β, IL-6, and IL-8 were measured in 20 and 22 patients who underwent orthotopic neobladder replacement using ileum and sigmoid colon, respectively, and all cytokine levels greater than␣5 pg/ml were defined as elevated. The outcomes were compared with respect to several parameters. Results The proportions of patients positive for urinary culture, pyuria, and bacteriuria in the ileal neobladder group were higher than those in the sigmoid neobladder group, but these differences were not significant. Urinary levels of IL-1β, IL-6, and IL-8 in the ileal neobladder group were significantly greater than those in the sigmoid neobladder group. Furthermore, the incidences of elevated urinary levels of IL-1β, IL-6, and IL-8 in both groups were not affected by age, postoperative period, residual urine volume or pyuria; however, the incidences of elevated urinary IL-6 levels significantly differed between patients with and without bacteriuria in the ileal neobladder group, while there was a significant difference in the incidences of elevated urinary IL-8 levels between patients with and without bacteriuria in the sigmoid neobladder group. Conclusions These findings suggest that chronic inflammation was more frequently observed in patients with ileal neobladder than in those with sigmoid neobladder, and that IL-6 and IL-8 were involved in persistent bacteriuria in patients with ileal and sigmoid neobladder, respectively.     

Soluble TNFα Receptors Are Increased in Chronic Renal Insufficiency and Hemodialysis and Inhibit Neutrophil Priming by TNFα

Abstract: The oxidative burst of neutrophils from azotemic patients is refractory to priming by tumor necrosis factor-α (TNFα). Soluble TNFα binding proteins (TNFR) accumulate in the plasma of azotemic patients. To test the hypothesis that these increased sTNFR concentrations inhibit TNFa priming of oxidative burst activity, we measured plasma sTNFR concentrations in nondialyzed azotemic patients, hemodialysis patients, and normal subjects, and determined TNFa priming of fMet-Leu-Phe-stimulated superoxide production in neutrophils incubated in plasma with differing levels of sTNFR. These sTNFR concentrations increased significantly as creatinine clearance decreased and were significantly greater in hemodialysis patients than could be accounted for by loss of renal function alone. TNFα primed superoxide production by normal neutrophils in normal plasma, but this effect was significantly reduced in plasma with increased concentrations of sTNFR. Neutrophils from azotemic and hemodialysis patients were refractory to priming by TNFα in autologous plasma, and incubation in normal plasma only partially corrected this defect. We conclude that sTNFR accumulate as a result of the loss of renal function and hemodialysis and inhibit TNFα priming of neutrophils in azotemic and hemodialysis patients, but that these cells also have an intrinsic functional defect.     

胆道术后腹腔引流液中炎性因子检测对胆瘘早期诊断的研究

目的通过观察胆道术后腹腔引流液中炎性细胞因子水平变化,衡量其作为早期预测和诊断胆瘘指标的意义。方法总结3227例胆道手术患者相关临床资料,观察胆瘘发生与年龄、性别、手术方式、手术时间等指标的关系,并于术后1,3,5d检测患者腹腔引流液和血清标本中IL-6,IL-8,IL-10,TNF-α和CRP变化,比较胆瘘组(17例)和非胆瘘组(3210例)上述指标的差异。结果胆瘘发生与患者年龄、性别、腔镜或开腹手术方式无关(P0.05),与手术时长短、术中出血量多少、胆总管直径大小有关(P0.05),其术后腹腔引流液细胞因子水平显著高于非胆瘘组和血清水平。结论腹腔引流液炎性细胞因子水平是反应腹腔内炎症的敏感指标,有助于早期发现胆瘘,避免严重后果。     

Blood leucocyte cytokine production after LPS stimulation at different concentrations of glucose and/or insulin

Background: Previous studies have indicated that alterations in blood glucose and/or insulin levels modify the inflammatory response. The purpose of this study was to elucidate whether increased levels of glucose and/or insulin influence the activation pattern of blood leucocytes and their production of cytokines in vitro .
Methods: Venous blood was obtained from eight healthy male volunteers after an overnight fast. Glucose and/or insulin were added to aliquots of whole blood to increase the blood glucose concentration by 5 or 20 mmol/l and/or the insulin concentration by 6 or 30 nmol/l, respectively, before stimulation with E. coli lipopolysaccharide (LPS) at concentrations of 10, 100 or 1000 ng/ml. The samples were subsequently incubated at 37 °C for 6 h before cytokine measurements. After centrifugation the levels of interleukins (IL)-1β, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α were measured in plasma using enzyme-linked immuno-sorbent assays. The results were compared with cytokine levels in parallel control samples to which only identical amounts of LPS were added.
Results: The LPS-stimulated production of IL-1β was significantly reduced by on average 26% in samples to which glucose 20 mmol/l was added; addition of insulin and/or glucose 5 mmol/l had no apparent effect on the IL-1β production at any LPS concentration. The levels of IL-6, IL-8, IL-10 and TNF-α were not manifestly altered by addition of glucose and/or insulin at any LPS concentration.
Conclusion: A substantial increase in blood glucose concentration changed the IL-1β production, but not the production of other cytokines, in response to LPS stimulation.     

Expression of transforming growth factor (TGF)-β1 mRNA and contractility of extracellular matrices in three-dimensional culture of rat peritoneal fibroblasts

Background. In a fibrotic process the interaction between resident cells and extracellular matrices is important in the control of cell function. Our preliminary experiments indicated that concentrated peritoneal dialysis effluent caused contraction of collagen matrices by peritoneal fibroblasts. In this study we attempted to mimic the inflammatory milieu present during peritoneal inflammation and assessed its effect on fibroblast activation. Methods. Rat peritoneal fibroblasts (RPFB) were isolated by a time-elapsed differential subculture from mixtures of primary cultures of peritoneal resident cells, and then cultured in collagen matrices. Various inflammatory mediators, known to be present in the peritoneal cavity during inflammation, (i.e., interleukin-6 [IL-6], IL-1β, and tumor necrosing factor (TNF)α were added to three-dimensional-RPFB cultures (1 × 10⁵/ml) prior to their incubation for either 48 h or 10 days. The contractility of collagen matrices over this time period was monitored, as was the expression of transforming growth factor (TGF)-β1 mRNA. Experimental conditions were: (i) control gels, (ii) gels with IL-6, (iii) gels with IL-1β, (iv) gels with TNFα, (v) gels with each cytokine plus glucose (90 mM). Results. With 48 h stimulation, a greater than tenfold increase in TGF-β1 mRNA expression (measured as the ratio to TGF-β1/glyceraldehyde 3-phosphate dehydrogenase [GAPDH] mRNA) was observed compared with the control, and this was accompanied by gel contraction. With 10-day stimulation, both IL-1β and TNFα suppressed the expression of TGF-β1 mRNA as well as suppressing gel contraction. There was a 30% to 40% gel contraction accompanied by elongation of RPFB morphology in the IL-6 and control groups. The addition of glucose promoted the extension of RPFB and gel contraction by up to 60% in both the IL-1β- and TNFα-supplemented groups. Conclusion. These in vitro findings suggest that a balance of inflammatory cytokines influences rat peritoneal fibroblast (RPFB) gene expression, causing changes in the interaction between extracellular matrices and peritoneal fibroblasts. Received: May 24, 1999 / Accepted: August 18, 1999     

Bone-Resorbing Cytokines from Peripheral Blood Mononuclear Cells after Hormone Replacement Therapy: A Longitudinal Study

Conflicting results have been reported in several cross-sectional studies measuring cytokine production from adherent monocytes in pre- and postmenopausal women. Furthermore, the target cells for the action of estrogen are still debated. We therefore assessed in a longitudinal manner the cytokine production from different fractions of peripheral blood mononuclear cells (PBMC) cultured for 48 h. PBMC were obtained from 30 postmenopausal women before and after 6 months of hormone replacement therapy (HRT). Women were randomly allocated to two groups: an adherent PBMC group (n= 20) and a total PBMC group (n= 9). After 6 months of treatment, urinary pyridinoline levels were markedly decreased in both groups (353 ± 24 vs 114 ± 13 μg/mmol creatinine and 325 ± 35 vs 164 ± 31 μg/mmol creatinine respectively, p<0.01). Culture supernatants were assayed for interleukin 1β (IL-1β), interleukin 6 (IL-6), soluble IL-6 receptor (IL-6rs) and tumor necrosis factor alpha (TNF-α). In the adherent PBMC group, HRT induced a nonsignificant trend toward decreased levels of IL-1β (35 ± 10 vs 13 ± 5 pg/ml), TNF-α (333 ± 58 vs 222 ± 30 pg/ml) and IL-6 (115 ± 70 vs 17 ± 10 pg/ml). In contrast, in the total PBMC group, HRT induced a consistent and dramatic decrease in levels of IL-1β (104 ± 22 vs 25 ± 8 pg/ml), IL-6 (5950 ± 1041 vs 1011 ± 361 pg/ml), IL-6rs (148 ± 33 vs 35 ± 12 pg/ml) (p<0.01) and TNF-α (1468 ± 315 vs 585 ± 207 pg/ml, p= 0.05). We then evaluated whether HRT had the same effect in vitro. Adherent or total PBMC of 8 postmenopausal women were cultured with or without 10⁻⁸M 17β-estradiol or tibolone for 48 h. Production of IL-1β, TNF-α, IL-6 and IL-6rs was not affected by the presence of 17β-estradiol or tibolone in cultures of these cell fractions. In conclusion, our data indicate that non-adherent PBMC could mediate the response to HRT. HRT may exert its action indirectly via noncirculating cells, as suggested by the absence of an in vitro effect. Received: 11 July 2000 / Accepted: 15 January 2001     

Adsorption of Complement, Cytokines, and Proteins by Different Dialysis Membrane Materials: Evaluation by Confocal Laser Scanning Fluorescence Microscopy

The membranes tested in the present study were cellulose triacetate (CTA), polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN). The adsorption by each membrane of albumin, IgG, C3a, interleukin-1β (IL-1β), interleukin-6 (IL-6), human neutrophil elastase (HNE), and tumor necrosis factor α (TNFα) was examined and semiquantitatively graded by confocal laser scanning fluorescence microscopy (CLSFM). After clinical use the dialyzers were treated with antibodies for these proteins and cytokines. Then the samples were incubated with fluorescein isothiocyanate-labeled anti-IgG antibody and observed by CLSFM. The changes in the blood levels of C3a and cytokines were also studied. In the CTA membrane, the adsorption of these substances, except for albumin and HNE, was less than in the synthetic membranes. The PAN membrane revealed the most abundant adsorption, especially for IL-1β, IL-6, and TNFα. Although a marked elevation of C3a in the blood was observed in the CTA membrane, considerable adsorption was evident in the PMMA and the PAN membranes. Because the changes in the blood levels could be affected by membrane adsorption, both the blood levels and the adsorption of the biocompatibility parameters should be evaluated when membrane biocompatibility is discussed.     

The effect of risedronate treatment on serum cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study

There is much evidence suggesting that the decline in ovarian function after menopause is associated with spontaneous increases in proinflammatory cytokines. Treatment with risedronate is accompanied by significant changes in bone turnover and bone mineral density. The objective of this study was to determine the effects of risedronate treatment on the level of serum cytokines including receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin among postmenopausal women with osteoporosis. The study group consisted of 61 postmenopausal women with osteoporosis. Patients were randomly divided in two groups: In group 1 (n = 41) postmenopausal women received oral risedronate (35 mg/week), calcium (1,000 mg/day), and vitamin D (400 IU/day) for 12 months. In group 2 (control group; n = 20) patients received only oral calcium (1,000 mg/day) and vitamin D (400 IU/day). Bone mineral density (BMD) of lumbar spine (L1–L4) and proximal femur were determined using dual X-ray absorptiometry at baseline and after one year. Venous blood samples were obtained for determination of serum cytokines including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), RANKL, osteoprotegerin, and markers of bone formation and resorption. Levels of serum cytokines were measured before therapy and after three and 6 months. Markers of bone metabolism were studied before therapy and after 6 months. In group 1 (risedronate plus calcium/vitamin D-treated patients), serum levels of RANKL and IL-1β significantly decreased and the level of osteoprotegerin significantly increased after three and 6 months, but no significant difference was found in TNF-α level. In group 2, however, the level of serum cytokines did not change after three and 6 months. In cases of bone turnover, both markers of bone resorption and formation significantly decreased after 6 months in group 1. In conclusion risedronate could improve osteoporosis by increasing osteoprotegerin and reducing RANKL and IL-1β.     

Evaluation of urinary IL-1α and IL-1β in gravid females and patients with bacterial cystitis and microscopic hematuria

Objectives: to determine IL-1α and IL-1β levels in patients with bacterial cystitis, microscopic hematuria, and gravid females relative to a control group of normal subjects. Methods: enzyme immunoassays were used to measure concomitantly urinary IL-1α and IL-1β in clean catch urine samples from normal subjects (n=31) and study patients (n=46). All normal subjects and patients underwent urinalysis, urine culture, and urine creatinine level determination. Since the IL-1α assay was developed for serum, the utility of the assay for urine specimens was unknown. The key parameters of urine collection, processing and sample storage for IL-1α were evaluated in detail. Results: mean values ± SEM (pg/mg) for IL-1α/Cr and IL-1β/Cr were control group (0.25 ± 0.10 and 0.17 ± 0.06), bacterial cystitis (9.97 ± 1.15 and 42.45 ± 1.86), and microscopic hematuria (2.81 ± 0.65 and 2.82 ± 0.70). Differences in cytokine levels between the control group and patients with either bacterial cystitis or microscopic hematuria were statistically significant for both IL-1α/Cr (P<0.026; P<0.007, respectively) and IL-1β/Cr (P<0.0004; P<0.014, respectively). IL-1β/Cr correlates better with pyuria than IL-1α/Cr (P=0.02 vs P=0.44). In gravid females, only IL-1α was significantly elevated relative to non-pregnant females (IL-1β elevation approached statistical significance). Gravid females with positive urine cultures could not be distinguished from those with negative cultures based on either interleukin (P>0.05). Conclusions: Significant elevations of IL-1α and IL-1β occur in patients with bacterial cystitis and microscopic hematuria. Correlation between pyuria and cytokine elevation was stronger for IL-1β than for IL-1α. Changes in IL-1α may reflect changes in the bladder epithelium rather than in the inflammatory leukocytes. The ability of IL-1α and IL-1β to serve as markers for bacterial cystitis in gravid females is diminished due to high basal levels during pregnancy. Received: 30 June 1997 / Accepted: 3 December 1997     

Effects of anaesthesia based on high versus low doses of opioids on the cytokine and acute-phase protein responses in patients undergoing cardiac surgery

Background : Cardiac surgery with cardiopulmonary bypass (CPB) evokes a systemic inflammatory response involving the proinflammatory cytokines tumor necrosis factor-α (TNFα), interleukin (iL)-1, IL-6, IL-8 and anti-inflammatory cytokines such as IL-10. Like IL-10, opioids downregulate the immune responses in vivo and in vitro, including the activity of the cytokine-producing monocytes and granulocytes. The proinflammatory cytokines are potent inducers of the hepatic acute-phase protein synthesis. The aim of the present study was to investigate if choice of anaesthesia, based on high-dose opioids (fentanyl) versus low-dose opioids influenced the release of IL-6, IL-8, and IL-10. Secondly, it was investigated whether serum amyloid P-component (SAP) is an acute-phase protein in man such as C-reactive protein (CRP), with which it is physically and structurally related. Methods : Sixteen patients submitted to elective coronary artery bypass grafting (CABG) surgery were randomized to either low-dose opioid anaesthesia consisting of thoracic epidural analgesia combined with inhalational anaesthesia (group I) or high-dose fentanyl anaesthesia (group II). From each patient 18 blood samples were taken perioperatively. Cytokine analyses were performed with ELISA, CRP and SAP mere measured with rocket immunoelectrophoresis (REI). Results : Surgery and CPB elicited a marked, transient and almost simultaneous proinflammatory and anti-inflammatory cytokine response with no differences between the groups. The cytokine levels returned to preoperative levels 1–3 d after operation. Anaesthesia and surgery did not affect SAP plasma levels while patients showed a major increase in CRP concentrations preceding the cytokine responses. Conclusion : CABG performed during two different anaesthetic techniques, high-dose fentanyl versus low-dose opioid anaesthesia, elicited a well-defined cytokine response with minor variation in the time course of each cytokine. The cytokine production was not modified by type of anaesthesia. Finally, SAP is not an acute-phase protein in men.     

Proinflammatory cytokines in cerebrospinal fluid in repair of thoracoabdominal aorta

BACKGROUND: Little is known about alterations of cytokine levels in cerebrospinal fluid (CSF) during thoracoabdominal aortic surgery. We measured perioperative CSF cytokine levels to determine their clinical significances. METHODS: Perioperative serum and CSF levels of cytokine were measured in 15 adult patients undergoing repair of the descending thoracic aorta (n = 4) or thoracoabdominal aorta (n = 11). All patients underwent prosthetic replacement and perioperative CSF drainage. Serum and CSF levels of tumor necrosis factor-alpha, Interleukin- (IL-) 1beta, IL-6, IL-8, IL-10, and IL-12 were measured before operation and at 0, 6, 12, 18, 24, 48, and 72 hours postoperatively using enzyme-linked immunosorbent assays. RESULTS: There were no hospital deaths, but 1 patient suffered paraplegia. Cerebrospinal fluid IL-8 levels peaked at immediately after operation (751.7 +/- 42.1 pg/mL versus preoperative levels, 54.9 +/- 24.6 pg/mL; p < 0.001), and the higher levels persisted for 72 hours. In contrast, serum IL-8 levels did not change and remained lower than CSF levels. The patient with paraplegia had the highest CSF IL-8 levels throughout the study period. Serum and CSF levels of tumor necrosis factor-alpha, IL-1beta, IL-6, and IL-12 did not significantly change. Serum and CSF levels of IL-10 were significantly elevated after operation compared with preoperative levels. In contrast to IL-8, serum IL-10 levels surpassed CSF levels. CONCLUSIONS: Cerebrospinal fluid IL-8 levels are significantly elevated in thoracoabdominal aortic operation, and may be the most sensitive to the inflammatory response in the ischemic spinal cord injury. Persistent elevation of CSF IL-8 levels may be predictive of further development of neurologic deficits, and a reduction of proinflammatory cytokine levels may be a beneficial effect of CSF drainage, but this requires further investigation.     

Hormone-cytokine response

Background: Changes in blood hormone and cytokine were investigated in patients who underwent laparoscopic cholecystectomy via insufflation (CO₂ group) vs those who had abdominal wall-lifting (Air group). Methods: Seventeen female patients with cholecystolithiasis were randomly divided into two groups. Peripheral blood samples were obtained during perioperative period, and plasma hormone levels (ACTH, cortisol) and serum cytokine levels (TNFα, IL-1β, IL-6, IL-10) were measured. Results: The number of circulating lymphocytes significantly decreased at 1 h after surgery in both groups, but the decrease in the CO₂ group was significantly smaller than that in the Air group. There was no significant difference in hormone elevation between groups. Serum concentrations of IL-6 and IL-10 in the Air group were significantly higher than in the CO₂ group. Conclusions: CO₂ insufflation may reduce cytokine production in laparoscopic cholecystectomy. Received: 10 November 1996/Accepted: 19 February 1997     

Prospective evaluation of the systemic immune response following abdominal, vaginal, and laparoscopically assisted vaginal hysterectomy

Background: Alterations in serum levels of cytokine interleukin-6 (IL-6) and acute-phase protein C-reactive protein (CRP) correlate directly with extent of tissue damage and inflammatory reaction. We therefore prospectively compared the postoperative levels of IL-6 and CRP following abdominal (AH), vaginal (VH), and laparoscopically assisted vaginal hysterectomy (LAVH). Methods: A total of 29 patients were included in the study (10 VH, 10 LAVH, 9 AH). Nine blood samples were taken from each patient at various time points before, during, and after surgery. CRP and IL-6 were measured under standardized conditions using ELISA and turbidometry. Results: Preoperative levels of IL-6 and CRP were low in all three patient groups. There was a significant increase in the IL-6 level in patients undergoing AH at the time of peritoneal closure that reached a maximum 2 h postoperatively and remained significantly elevated for 12 h postoperatively when compared to the IL-6 levels of patients undergoing VH or LAVH (p < 0.05). The levels of the IL-6 time courses differed significantly among the three operative procedures (p = 0.013). In contrast, the levels of the CRP time courses did not differ significantly (p = 0.066); however, CRP expression was elevated 36 h postoperatively in patients undergoing AH, as compared with those undergoing VH. Conclusion: Elevated IL-6 levels subsequent to AH may reflect significantly greater tissue damage in these patients than in patients who undergo VH or LAVH. LAVH should therefore be considered in cases that cannot be managed by the vaginal route alone. apd: 13 March 2001     

Cytokine gene polymorphisms and the inflammatory response to abdominal aortic aneurysm repair

BACKGROUND: Cytokines are key mediators of the inflammatory response to surgery and polymorphic sites in their genes have been shown to affect cytokine production in vitro. The aim of this study was to determine whether cytokine gene polymorphisms affect cytokine production in vivo in patients undergoing abdominal aortic aneurysm (AAA) repair. METHODS: One hundred patients admitted for elective AAA repair had plasma levels of interleukin (IL) 1beta, IL-6, IL-10 and tumour necrosis factor (TNF) alpha measured at induction of anaesthesia and 24 h after operation. Genotypes for each patient were determined using induced heteroduplex genotyping for the following loci: IL-1beta + 3953, IL-6 - 174, IL-10 - 1082/-592 and TNF-alpha - 308. RESULTS: Patients with an IL-10 - 1082 A allele had a significantly higher IL-10 response to surgery than those without an A allele (P = 0.030) and there was also a significant difference in IL-10 response between patients with IL-10 - 1082 AA genotypes and those with GG genotypes (P = 0.030). CONCLUSION: Elective AAA repair results in a measurable cytokine response. In this study the magnitude of this response was not affected by the individual patient's cytokine gene polymorphisms.     

Release of (1-->3)-beta-D-glucan from depth-type membrane filters and their in vitro effects on proinflammatory cytokine production

To clarify the origin of (1-->3)-beta-D-glucan in blood products and assess the biological activity of filter extracts, we evaluated (1-->3)-beta-D-glucan extraction from depth filters used to process blood products and their in vitro effects on proinflammatory cytokine production from macrophages. Cellulose or nylon filters were analyzed for (1-->3)-beta-D-glucan using the Fungitec G test. To evaluate the biological activity of the filter extracts, Mono Mac 6 cells (a human macrophage cell line) were cultured with filter extracts with or without lipopolysaccharide, and tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) concentrations in the culture media were measured. (1-->3)-beta-D-Glucan was released from seven cellulose filters but the nylon filter level was undetectable. Proinflammatory cytokine production ranged from 74.3% to 119.0% of the control for TNF-alpha and 81.2% to 115.9% for IL-1beta. TNF-alpha and IL-1beta levels were low without lipopolysaccharide. The data indicate that (1-->3)-beta-D-glucan in blood products is contaminated with the depth filters and that these filter extracts modulate proinflammatory cytokine production from macrophages.