Th1-like and Th2-like cytokines in patients undergoing open versus laparascopic cholecystectomy

The advantages of laparoscopic (LC versus, open cholecystectomy (OC) seems to be related to minimal invasive procedure and to the moderate inflammatory response. The aim of this study is to define the involvement of Th1 (IFN-gamma) and Th2 (IL-4, IL-6, IL-10, IL-13) cytokines production in vivo and in vitro in patients undergoing OC or LC. In 42 patients undergoing LC (n = 22) and OC (n = 20) Th1-like and Th2-like was evaluated before operation and at 6, 24 and 48 hours after operation for white blood cell counting and cytokines (IL-4, IL-6, IL-10, IL-13, IFN-gamma, TNF-alpha) in the sera and in the supernatants from circulating mononuclear cells stimulated with phytohemagglutinin or lipopolysaccharide. The acute phase response cytokine, IL-6, appeared significantly increased following OC than after LC. All other cytokines did not very significantly. In vitro data shows a reduction of IFN-gamma and increase in Th2-like cytokines in OC patients compared with the basal value. In LC subjects we observed an high production of IFN-gamma associated to an increase of Th2-like cytokines, like IL-10 and IL-13, even though IL-4 and IL-6 were unmodified. In contrast to OC, LC did not significantly affect immunocompetence, maintaining a moderate inflammatory response and an adequate balance between Th1 and Th2 cytokine. Furthermore, the strong activation of cells producing Th1-like cytokines in LC patients following mitogen activation indicated a consistent anti-microbial activity, that was not detectable in OC patients, that showed after activation only a Th2 response.     

Pseudomonas aeruginosa infection,but not mono or dual-combination CFTR modulator therapy affects circulating regulatory T cells in an adult population with cystic fibrosis

BackgroundChronic infection and an exaggerated inflammatory response are key drivers of the pathogenesis of cystic fibrosis (CF), especially CF lung disease. An imbalance of pro- and anti-inflammatory mediators, including dysregulated Th2/Th17 cells and impairment of regulatory T cells (Tregs), maintain CF inflammation. CF transmembrane conductance regulator (CFTR) modulator therapy might influence these immune cell abnormalities.MethodsPeripheral blood mononuclear cells and serum samples were collected from 108 patients with CF (PWCF) and 40 patients with non-CF bronchiectasis. Samples were analysed for peripheral blood lymphocytes subsets (Tregs; Th1-, Th1/17-, Th17- and Th2-effector cells) and systemic T helper cell-associated cytokines (interleukin [IL]-5, IL-13, IL-2, IL-6, IL-9, IL-10, IL-17A, IL-17F, IL-4, IL-22, interferon-γ, tumour necrosis factor-α) using flow cytometry.Results51% of PWCF received CFTR modulators (ivacaftor, ivacaftor/ lumacaftor or tezacaftor/ ivacaftor). There were no differences in proportions of analysed T cell subsets or cytokines between PWCF who were versus were not receiving CFTR modulators. Additional analysis revealed lower percentages of Tregs in PWCF and chronic pulmonary Pseudomonas aeruginosa infection; this difference was also present in PWCF treated with CFTR modulators. Patients with non-CF bronchiectasis tended to have higher percentages of Th2- and Th17-cells and higher levels of peripheral cytokines versus PWCF.ConclusionsChronic P. aeruginosa lung infection appears to impair Tregs in PWCF (independent of CFTR modulator therapy) but not those with non-CF bronchiectasis. Moreover, our data showed no statistically significant differences in major subsets of peripheral lymphocytes and cytokines among PWCF who were versus were not receiving CFTR modulators.     

Effects of dexmedetomidine on the ratio of T Helper 1 to T Helper 2 cytokines in patients undergoing laparoscopic cholecystectomy

Study ObjectivesTo investigate the effect of dexmedetomidine on T helper 1 (Th1) and T helper 2 (Th2) cytokines and their ratio during and after surgery.DesignSingle-blinded, randomized, placebo-controlled clinical comparison study.SettingAcademic medical center.Patients46 adult, ASA physical status 1 and 2 patients scheduled for laparoscopic cholecystectomy.InterventionsPatients were randomized to two groups: the dexmedetomidine group (n = 23), in which dexmedetomidine was infused with a 1.0 μg/kg loading dose followed by infusion of 0.5 μg/kg/h; or the saline group (n = 23).MeasurementsInterferon-gamma (IFN-gamma) and interleukin-4 (IL-4) as Th1 and Th2 cytokines, respectively, were quantified three times: after induction of anesthesia (T0), at the end of peritoneal closure (T1), and 60 minutes after surgery (T2). The IFN-gamma/IL-4 ratio was then calculated.Main ResultsThe dexmedetomidine group displayed higher levels of IFN-gamma at T1 and T2 (42.30 pg/dL vs 6.91 pg/dL at T1 [P = 0.025]; 40.51 pg/dL vs 8.29 pg/dL at T2 [P = 0.030]) than the saline group. The dexmedetomidine group was also associated with higher ratios of IFN-gamma/IL-4 (1.22 vs 0.32, respectively, at T1 [P = 0.012]; 1.53 vs 0.13, respectively, at T2 [P = 0.012]).ConclusionsDexmedetomidine plays an immunomodulatory role, shifting the Th1/Th2 cytokine balance toward Th1 in patients with surgical and anesthetic stress.     

T lymphocyte subsets and Th1/Th2 balance after laparoscopy-assisted distal gastrectomy

Background: Laparoscopic surgery provides for a less invasive procedure than open surgery in patients with gastric cancer, but the immune responses after laparoscopic surgery for early gastric cancer remain unknown. Methods: Peripheral blood mononuclear cells from 20 patients with early gastric cancer who underwent laparoscopy-assisted distal gastrectomy (LADG) or open distal gastrectomy (ODG) were obtained; the cell surface molecules and intracellular cytokines (IFN-gamma and IL-4) were measured by flow cytometry. Results: The populations of T lymphocytes after LADG, including CD3-, 4-, 8-, 57-, and HLA-DR-positive lymphocytes, showed patterns similar to those after ODG. The production of IFN-gamma as Th1 cell function decreased significantly on the third postoperative day after ODG but increased after LADG. The production of IL-4, representing Th2 cell function, increased postoperatively after ODG but not after LADG. Conclusions: When compared with ODG, LADG contributes to the preservation of postsurgical Th1 cell-mediated immune function.     

Effect of renal dialysis therapy modality on T cell cytokine production.

INTRODUCTION: Dialysis has been associated with acute changes in the complement activation status, granulocyte markers, macrophage function, T cell activation and the release of pro-inflammatory cytokines. The most common analysis of cytokine production in patients on dialysis has focused on the changes in monokines (particularly IL-1 and TNF alpha), however it is becoming clear that T cell cytokines play a major role in the impaired lymphocyte function of dialysis patients. METHODS: To assess the effect of dialysis modality on T cell function we analysed the ability of T cells within peripheral blood mononuclear cell populations (PBMC) to produce cytokines after mitogen (phorbol-12-myristate-13-acetate; PMA and lonomycin; I) stimulation in patients on peritoneal dialysis (PD) compared to low flux haemodialysis (HD) and normal individuals (controls). RESULTS: In control PBMC, PMA + I stimulation significantly increased the percentage of CD3+ cells expressing IL-2, IFN gamma, TNF alpha, IL-4 and IL-10, as expected. However, although mitogen stimulation significantly enhanced the percentage of the classical Th1 cytokines (IL-2, IFN gamma and TNF alpha) in the low flux HD PBMC, it had no effect on CD3+ IL-2 or CD3+ TNF alpha producing cells in the PD group. In contrast, the percentage of T cells producing Th2 cytokines (IL-4 and IL-10) could not be consistently enhanced by mitogen in either dialysis group. CONCLUSIONS: We suggest that PD alters the ability of T cells to produce cytokines, possibly by causing an 'exhaustion' of the Th1 cells, thereby preventing cells to produce cytokine on ex vivo stimulation. Furthermore, since T cells from both low flux HD and PD groups could not be induced to produce Th2 cytokines we suggest that uraemia or dialysis per se inhibits T cells from producing Th2 cytokines.     

Melanoma skews dendritic cells to facilitate a T helper 2 profile

BACKGROUND: Patients with progressing melanoma have a circulating cytokine profile reflecting a T helper cell type 2 (Th2) imbalance, while patients responding to therapy favor a Th1 profile. The aim of this study was to determine the role of circulating dendritic cells (DCs) in mediating this imbalance. METHODS: Isolated human peripheral blood mononuclear cells (PBMCs) were exposed to cell-free melanoma-conditioned medium (MCM) or control fibroblast-conditioned medium before stimulation. In separate experiments, isolated circulating DCs were exposed to MCM before addition of T cells. DC maturation and function were determined. Mixed leukocyte response T-cell proliferation was quantified and supernatants were assayed for Th1 (interleukin [IL]-2 and interferon gamma) and Th2 (IL-4, IL-5, and IL-10) cytokines. RESULTS: PBMCs exposed to MCM produced significantly more Th2-type cytokines (IL-4, IL-5, and IL-10) over time than those exposed to control medium. DCs exposed to MCM before addition of T cells, produced a similar pattern of a sustained longer term Th2 response after an initial burst of IL-2. Exposure to MCM did not significantly affect DC maturation or IL-12 production. T-cell proliferation did not change significantly in the mixed leukocyte response, however, the percentage of viable CD4+ T cells in the MCM-treated group was significantly less than control (37 vs 50%, P < .05). CONCLUSIONS: Exposure of PBMCs to melanoma produces a Th2-type cytokine profile, which may be, in part, facilitated by DCs.     

Intracellular cytokine repertoire in different T cell subsets from patients with sarcoidosis

BACKGROUND: Pulmonary sarcoidosis is characterised by a mononuclear alveolitis with a predominance of CD4+ T cells and macrophages. We determined the intracellular expression of interferon (IFN)gamma, interleukin (IL)-2, tumour necrosis factor (TNF)alpha, IL-4, IL-5 and IL-10 in CD4+ and CD8+, naive and memory lymphocytes from blood and bronchoalveolar lavage (BAL) fluid using three colour flow cytometry. METHODS: Eighteen untreated patients with pulmonary sarcoidosis were evaluated and stratified according to whether they had acute or chronic disease. RESULTS: Significantly more T cells expressed Th1 than Th2 type cytokines in both BAL fluid and peripheral blood samples, regardless of clinical presentation. Significantly greater proportions of T cells secreted Th1 type cytokines in BAL fluid than in peripheral blood. Th1 type cytokines were more frequently expressed by peripheral and alveolar T cells in acute disease than in chronic disease. There were no significant differences between CD4+ and CD8+ T cells. Concerning naive and memory lymphocytes, significantly higher CD45RO:CD45RA ratios were found in BAL fluid than in blood, and increased expression of Th2 type cytokines was found in peripheral compared with alveolar memory T cells. CONCLUSIONS: Our data support the immunopathogenetic concept of Th1/Th2 imbalance and compartmentalisation in pulmonary sarcoidosis and suggest that the cytokine patterns change during the course of disease. Expression of Th2 type cytokines in memory lymphocytes is decreased in the alveolar compartment compared with peripheral blood.     

An alternate mechanism of glucocorticoid anti-proliferative effect: promotion of a Th2 cytokine-secreting profile

Glucocorticoids (GCs) are used as immunosuppressive and anti-inflammatory agents in organ transplantation and in treating autoimmune diseases and inflammatory disorders and they exert their effects by several mechanisms, the most significant of which is inhibition of cytokine production and action. Recent reports suggested that GCs inhibit cytokine expression indirectly through promotion of a T helper cell type 2 (Th2) cytokine-secreting profile, thereby resulting in preferential blockade of pro-inflammatory monokine and T helper cell type 1 (Th1) cytokine expression. The target of GCs appeared to be monocytes macrophages, whereby altered regulation of interleukin (IL)-1/IL-1 receptor antagonist (IL-1ra), coupled with profound blockade of IL-12 synthesis and inhibition of interferon (IFN)-gamma-induced major histocompatibility complex (MHC) class II expression, lead to a preferential cognate stimulation of Th2 cells at the expense of Th1 cells. It is possible that this may have involved the expansion of a Th2-cell pool or, in addition, frank stimulation of uncommitted naive CD4 + T cells toward the Th2 lineage. In addition, GCs may have blocked Th1 cytokine expression, thereby inhibiting ongoing Th1 cytokine secretion, and consequently provided for the unimpeded production of Th2 cytokines. Collectively, this indicates that, in exerting their anti-proliferative effects, GCs act indirectly by altering Th1/Th2 cytokine balance, blocking the (pro-inflammatory) Th1 program and favoring the (anti-inflammatory) Th2 program.     

Increased intracellular pro- and anti-inflammatory cytokines in bronchoalveolar lavage T cells of stable lung transplant patients

BACKGROUND: Allograft rejection remains a major cause of morbidity and mortality following lung transplantation and is associated with an increased expression of T-cell proinflammatory cytokines. We have recently shown that peripheral blood T-cell proinflammatory cytokine production was significantly reduced in stable lung transplant patients consistent with immunosuppression therapy. However, analysis of inflammatory cytokine profiles in bronchoalveolar lavage (BAL) T cells may be more relevant than peripheral blood T cells for assessing graft status. METHODS: To investigate the immunomodulatory effects of currently used immunosuppressive regimens on BAL T-cell cytokine production, whole blood and BAL from stable lung transplant patients and control volunteers was stimulated in vitro and cytokine production by CD8+ and CD4+ T-cell subsets determined using multiparameter flow cytometry. RESULTS: There was a significant decrease in T-cell proinflammatory cytokine production in BAL compared with blood from control subjects but not transplant patients. Anti-inflammatory cytokine IL-4 was increased in BAL compared with blood from both groups. There was a significant increase in IFNgamma, IL-2, IL-4, TGFbeta, and TNFalpha production by CD8 T cells and IFNgamma and TNFalpha production by CD4 T cells in BAL from transplant patients compared with controls. CONCLUSIONS: We have shown decreased T-cell pro- and anti-inflammatory cytokine production in BAL compared with blood in control subjects but not in stable lung transplant patients. Current immunosuppression protocols have limited effect on T-cell proinflammatory cytokine production in BAL but do upregulate anti-inflammatory cytokines IL-4 and TGFbeta. Drugs that effectively reduce T-cell proinflammatory cytokine production in BAL may improve current protocols for reducing graft rejection in these patients.     

Analysis of type T1 and T2 cytokines in patients with prostate cancer

BACKGROUND: It has been proposed that a dysregulation in the balance between type T1 (IL-2, IFN-gamma) and type T2 (IL-4, IL-10) cytokines may be implicated in the development of cancer. METHODS: We determined the expression of IL-2, IL-4, IL-10, and IFN-gamma in CD4 and CD8 lymphocytes by flow cytometry in 12 patients with prostate cancer and in 7 healthy subjects. In addition to the basal expression of these cytokines, their expression was also determined, following stimulation of lymphocytes with PMA (phorbol 12-mystirate 13 acetate) and ionomycin. RESULTS: The basal expression of cytokines was scarce, while following stimulation this increased markedly. On the other hand, there was a dysregulation in the balance between T1 and T2 lymphocytes in patients with prostate cancer. To this effect, in relation to healthy subjects, we observed an increase in IL-10 expression and a decrease in IL-2 expression. CONCLUSIONS: The disequilibrium observed in the balance between type T1 and type T2 cytokines may be implicated in the evolution of neoplastic disease.     

Cytokine production in surgical stress

Surgical injury influences the function of mononuclear cells, leading to various systemic responses. Proinflammatory cytokines such as tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1, -6, -8, and the antiinflammatory cytokine IL-10, which are mainly produced by mononuclear cells, are known to play an important role in the response to and pathogenesis of surgical stress. TNF alpha production by monocytes is extremely upregulated, but monocyte HLA-DR antigen expression is suppressed in patients with surgical stress. While production of Th1 cytokines such as IL-12 and interferon-gamma by mononuclear cells is suppressed, production of Th2 cytokines and IL-10 is upregulated during surgical stress. Immune suppression following surgical stress has been clarified recently in terms of Th1 and Th2 cytokine production balance mainly caused by mononuclear cells. It is thought to be very important to maintain immunological function after surgical stress by controlling cytokine production and balance.     

晚期肺癌患者化疗前后细胞免疫功能及T细胞分泌细胞因子的变化

目的:探讨晚期肺癌患者化疗前后外周血中T细胞免疫功能及其分泌细胞因子水平的变化.方法:通过流式细胞仪检测57例晚期肺癌患者和22例健康体检者CD4+T淋巴细胞和CD8+T淋巴细胞在外周血单核细胞(PBMC)中所占比例以及外周血CD4+T细胞分泌细胞因子水平的变化.结果:晚期肺癌患者化疗前CD4+T细胞在PBMC中所占比例、CD4+T细胞与CD8+T细胞比值均低于健康人(P＜0.001),化疗后均较化疗前明显升高(P＜0.01或P＜0.001):化疗前CD8+T细胞在PBMC中所占比例高于健康人(P＜0.001),而于化疗后较化疗前明显下降(P＜0.05).治疗前后患者血清中CD4+T细胞分泌Th1细胞因子(IFN-y、TNF-α、IL-2)和Th2细胞因子(IL-4、IL-6、IL-10)水平均无明显变化(P＞0.05).结论:化疗能够增加肺癌患者外周血中CD4+T细胞所占比例,但对Th1、Th2所分泌的相关细胞因子水平影响不大.     

Morbidly obese human subjects have increased peripheral blood CD4+ T cells with skewing toward a Treg- and Th2-dominated phenotype

Obesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We determined all major T-cell subpopulations via six-color flow cytometry, including CD8+ and CD4+ T cells, CD4+ T-helper (Th) subpopulations, and natural CD4+CD25+FoxP3+ T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-β (TCRB) repertoire (GeneScan analysis) were performed. In addition, we determined plasma levels of proinflammatory cytokines and cytokines associated with Th subpopulations and T-cell proliferation. Morbidly obese subjects had a selective increase in peripheral blood CD4+ naive, memory, natural CD4+CD25+FoxP3+ Treg, and Th2 T cells, whereas CD8+ T cells were normal. CD4+ and CD8+ T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. CD4+ T-cell numbers correlated positively with fasting insulin levels. The peripheral blood T-cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute. This is associated with increased CD4+ T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point.     

Diminished interleukin-6 and C-reactive protein responses to laparoscopic versus open cholecystectomy

BACKGROUND: Cytokines and their inhibitors are thought to be involved in many of the pathophysiological changes associated with trauma and infection. The magnitude of the trauma and the degree of tissue damage have an impact on the trauma response. The purpose of the study was to examine cytokine and hormonal responses to elective cholecystectomy and the extent to which these responses are influenced by the surgical procedure employed. METHODS: Sixteen patients, ASA grades I and II, were studied: 8 of them underwent laparoscopic cholecystectomy while the remaining 8 were operated on using the open technique. Systemic concentrations of tumour necrosis factor alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL-6), cortisol, epinephrine and norepinephrine were measured before and during the operation and subsequently for up to 48 h postoperatively. The degree of pain and fatigue were recorded during the study period. RESULTS: The preoperative levels of cytokines and hormones were all similar in the groups. Concentrations of TNF and IL-1 were detected only sporadically. The rise in plasma IL-6 was less marked following laparoscopic than after open cholecystectomy. However, the hormonal response was quite similar in the two groups. Pain and fatigue scores were lower (P < 0.05-0.01) in the laparoscopic group than in the open surgery group. CONCLUSION: In summary, cholecystectomy, irrespective of whether it was performed using the laparoscopic or open technique, was followed by a trauma response and increased pain and fatigue. However, the magnitude of stress, pain and fatigue was less pronounced in laparoscopic cholecystectomy patients. Concentrations of IL-6 seem to be more sensitive when it comes to delineating the trauma response than systemic norepinephrine and epinephrine levels.     

Evolving management of mildtomoderate gallstone pancreatitis

The objective of this study was to describe recent trends in the management of mild-to-moderate gallstone pancreatitis and assess patient outcomes. Acute gallstone pancreatitis has traditionally been managed with open cholecystectomy and intraoperative cholangiography during the initial hospitalization. The popularization of endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy has made a reassessment necessary. Two consecutive time periods were retrospectively analyzed: prior to laparoscopic cholecystectomy (prelaparoscopic era [PLE]) and after the diffusion of laparoscopic cholecystectomy (laparoscopic cholectomy era [LCE]). There were 35 patients in the PLE group and 58 in the LCE group. LCE patients waited 37.1 +63 days from admission until cholecystectomy, compared to 9.8 +14.8 days in the PLE group (P = 0.04). Biliary-pancreatic complications occurred in 24% of LCE patients and only 6% of PLE patients (P = 0.05), nearly always while they were awaiting cholecystectomy (P = 0.009). Patients in either time period who underwent cholecystectomy with intraoperative cholangiography developed less pancreatic-biliary complications than those who underwent ERCP prior to cholecystectomy, with or without sphincterotomy. Delaying the interval from pancreatitis to laparoscopic cholecystectomy beyond historical values is associated with a greater risk of recurrent biliary-pancreatic complications, which are not prevented by the use of ERCE Early cholecystectomy with intraoperative ductal evaluation is still the approach of choice. Drs. J.S. Barkun and A.N. Barkun are Chercheurs Cliniciens Boursier of the Fonds de la Recherche en Sant6 du Qurbec. Dr. S.M. Mehta is the recipient of an American Digestive Health Foundation/American Society of Gastrointestinal Endoscopy Training Award.     

Transfer of allograft specific tolerance requires CD4+CD25+T cells but not interleukin-4 or transforming growth factor-beta and cannot induce tolerance to linked antigens

BACKGROUND: The mechanisms by which CD4+T cells, especially CD4+ CD25+T cells, transfer allograft specific tolerance are poorly defined. The role of cytokines and the effect on antigen-presenting cells is not resolved. METHODS: Anti-CD3 monoclonal antibody (mAb) therapy induced tolerance to PVG heterotopic cardiac transplantation in DA rats. Peripheral CD4+T cells or CD4+ CD25+ and CD4+ CD25-T cell subsets were adoptively transferred to irradiated DA hosts grafted with PVG heart grafts. For specificity studies, tolerant CD4+T cells were transferred to hosts with Lewis or (PVGxLewis)F1 heart grafts. Cytokine mRNA induction and the requirement for interleukin (IL)-4 and transforming growth factor (TGF)-beta in the transfer of tolerance was assessed. RESULTS: CD4+T cells transferred specific tolerance and suppressed na?ve CD4+T cells capacity to effect rejection of PVG but not Lewis grafts. (PVGxLewis)F1 grafts had a major rejection episode but recovered. Later these hosts accepted PVG but not Lewis skin grafts. Adoptive hosts restored with tolerant or na?ve cells had similar levels of mRNA expression for all Th1 and Th2 cytokines and effector molecules assayed. Transfer of tolerance by CD4+T cells was not blocked by mAb to IL-4 or TGF-beta. CD4+ CD25-T cells from either na?ve or tolerant hosts effected rejection. In contrast neither tolerant nor na?ve CD4+ CD25+T cells restored rejection. CONCLUSIONS: Specific tolerance transfer required CD4+ containing CD4+ CD25+T cells. An inflammatory response with induction of mRNA for Th1 and Th2 cytokines plus cytotoxic effector molecules occurred, but IL-4 and TGF-beta were not essential. Inhibition of antigen presenting cells was not the sole mechanism as there was no linked tolerance.     

Pro-inflammatory and anti-inflammatory circulating cytokines and periprosthetic osteolysis

We investigated the circulating levels of the main cytokines involved in bone resorption (IL-1beta, IL-6, TNF-alpha), prostaglandins (PGE2) and metalloproteases (MMP-1), as possible early markers of osteolysis, in the serum of eight patients with periprosthetic osteolysis and ten patients without osteolysis. All had received a cementless hip prosthesis (ABG-1). We also assessed the serum levels of IL-1 and TGF-beta anti-inflammatory cytokines exerting protective effect on bone resorption. The mean serum levels of IL-1beta, IL-6, TNF-alpha, TGF-beta, MMP-1, and PGE2 in patients with periprosthetic osteolysis did not differ significantly from those of patients without osteolysis or from those of normal controls. IL-11 serum levels were not detectable at all in any of the patients, while they were detected within normal reference values in the control subjects (significant inverse correlation). We believe that circulating cytokines cannot be regarded as markers of osteolysis, a condition characterised by a local inflammation without systemic signs of inflammation. On the contrary, the undetectable levels of IL-11 in implanted patients could provide evidence for a lack of balance between pro- and anti-inflammatory cytokines in these patients.     

The effect of anaesthesia and surgery on plasma cytokine production

The aim of this study was to investigate cytokine production in response to anaesthesia [total intravenous anaesthesia (TIVA) with propofol, sufentanil and atracurium] and surgery (laparoscopic vs. open cholecystectomy). Forty adult patients, ASA I-II, undergoing elective laparoscopic (group 1) or open (group 2) cholecystectomy were studied. Venous blood samples for measurement of interleukin (IL)-1beta, IL-2, IL-4, IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were taken before the induction of anaesthesia, pre-incisionaly, at the end of anaesthesia and surgery and 24-h postoperatively. Pre-incisionaly, in both groups, IL-1beta, IL-4, IL-6, TNF-alpha and IFN-gamma did not show a significant change, whereas IL-2 showed a significant decrease (p < 0.005 in group 1 and p < 0.001 in group 2) compared with pre-induction levels. By the end of anaesthesia and surgery, IL-1beta, IL-2, IL-4, IL-6 and TNF-alpha showed a significant increase in group 2 (p < 0.005 for IL-1beta, IL-2 and IL-4, and p < 0.05 for IL-6 and TNF-alpha); while in group 1, only IL-2 showed a significant increase (p < 0.01) and IFN-gamma showed a significant decrease (p < 0.05) compared with pre-incisional levels. By 24-h postoperatively, IL-1beta, IL-4, IL-6 and TNF-alpha had decreased significantly in group 2 (p < 0.005 for IL-4 and p < 0.05 for the others); whereas in group 1, IL-2 and IFN-gamma showed a significant increase (p < 0.005) compared with the end of anaesthesia and surgery level. In conclusion, TIVA with propofol, sufentanil and atracurium does not seem to have a significant effect on IL-1beta, IL-4, IL-6, TNF-alpha and IFN-gamma release. IL-2 was the only cytokine to show a significant decrease due to the effect of anaesthesia alone in both groups. The cytokine response to open cholecystectomy stimulated both the pro-inflammatory (IL-1beta, IL-6 and TNF-alpha) and the anti-inflammatory (IL-4) components, while this response was absent in laparoscopic cholecystectomy.