It is well established that major surgery, anaesthesia, and sedation compromise a wide range of immune function that may predispose patients to postoperative infections, septic complications, and tumour spread. The immunosuppressive effects of general anaesthesia are quite different and depend on the used anesthetic agents, dose and combinations. We tested the hypothesis that perioperative lymphocytopenia is due to apoptosis of these cells induced by balanced anesthesia. The relation of lymphocyte apoptosis to the anaesthesiological stress and concentrations of the main pro-and anti-inflammatory cytokines was also investigated. Based on the results we concluded that balanced anaesthesia used in the present study induced lymphocytopenia by activation of apoptosis of these cells which was due to the combined apoptogenic effects of halothane, fentanyl, and pancuronium, but neither to the anaesthesia-related stress-response nor to changes in the main pro-and antiinflammatory cytokines TNF-alpha and IL-10. Total lymphocyte count was diminished on the expense of B-lymphocytes without significant changes in CD 5+ and CD 8+ cells. Clinical implications: balanced anaesthesia disturbs normal humoral immune response by decreasing the count of Blymphocytes for minimum 24 hours after anesthesia.

The main purpose of this study was to investigate serum neopterin levels in workers exposed to coal and asbestos dust and to compare it to the levels found in silicosis patients and in a control group. Methods: Serum neopterin was measured in 190 workers exposed to inorganic dust, in 95 patients with silicosis and in 16 control subjects. Depending on characteristics of the dust the surveyed workers were divided into three groups: Group I (44) – exposed to dust containing less than 2% free crystalline silica, Group II (94) - exposed to dust containing more than 2% FCS and Group III (52) exposed to asbestos dust. Neopterin was determined by ELISA method, kit DRG Diagnostics, Germany in ng/mL. Results: We found higher levels of neopterin in workers exposed to dust (3,26 ± 0,57 ng/mL) compared to the control group (1,56 ± 0,38 ng/mL) and to the patients with silicosis (2,84 ± 1,19 ng/mL). Serum neopterin was significantly higher in workers from Group II (3,32 ± 0,77 ng/mL) and Group III (3,20 ± 0,48 ng/mL) compared to those from Group I and the controls. Conclusions: These results confirm the involvement of macrophages and cell-mediated immune reactions in the pathogenesis of pulmonary fibrosis in the development of pneumoconioses. Levels of neopterin in workers exposed to asbestos dust were examined for the first time and were found to be significantly higher than those of the control group.

The immunomodulatory properties of bioactive agents include the ability to induce cytokine production by the activated target cell. The effect of immunomodulatory C3 binding glycoprotein isolated from Cuscuta europea on the induction of human PBMC cytokine synthesis and the cell viability was investigated. Isolated PBMC from healthy donors were cultured for 24 It with C3bgp. We also studied the influence of C3bgp on the cytokine production in LPS, PHA, PWM and Dex treated PBMC. The quantitative determination of TNF-alpha, IL-12, IL-6 and IL-10 was performed in culture supernatant by ELISA.Results obtained demonstrated that C3bgp induced proinflammatory and immunoregulatory cytokine production, in the highest degree IL-12, followed by IL-6 and in lower degree TNF-alpha. IL-12 quantity was significantly increased in C3bgp stimulated cultures in comparison with LPS, PHA and PWM stimulated PBMC. C3bgp also increased IL-12 in PHA or PWM stimulated cultures, but not in LPS stimulated culture. C3bgp significantly increased IL-6 production compared to the PHA and PWM but not to LPS stimulation. On the other side, C3bgp inhibited IL-10 production after LPS, PHA and PWM stimulation. Cell viability in C3bgp stimulated cultures retained on the same level from 72 to 120 h of culturing, in contrast to LPS and PHA stimulated cultures.Based on the results presented, we conclude that the C3bgp exhibited immunomodulatory properties on the human PBMC. The ability of PDTC and Dex to down-regulate the effect of C3bgp on the proinflammatory cytokine production suggests that a part of the mechanism of action of C3bgp is mediated through NF-kappaB signal transduction pathway. (C) 2004 Elsevier B.V. All rights reserved.

OBJECTIVE:To study IL-6, IL-10, IL-12 levels and circulating immune complexes (CIC) containing IgG, IgM or IgA in sera of 14 TAO patients and 12 healthy blood donors. To evaluates the ability of TAO PBMC to produce IL-6, IL-10, IL-12, as well as to detect PBMC apoptosis after stimulation with different stimuli.METHODS:In vitro stimulation of PBMC with lypopolysaccharide (LPS), phytohemagglutinin (PHA), C3 binding glycoprotein from uscuta europea (C3bgp), pokeweed mitogen (PWM), and dexamethasone (DM) were performed. The quantities of the secreted cytokines in sera and in culture supernatants, as well as CIC were detected by ELISA. The apoptosis was assessed according to nuclear morphology, after acridine orange staining, by fluorescence microscopy.RESULTS:Significantly higher IL-6 levels in the patients', than in the controls' sera was found. An increased production of IL-6 and IL-12 in TAO PBMC supernatants was detected, regardless of the stimuli used. A hyporeactivity of TAO PBMC toward IL-10 production was found after C3bgp, LPS, PHA and PWM stimulation, compared to the controls' PBMC. The spontaneous and induced apoptosis was significantly higher in TAO compared to the control group. Increased CIC quantities were detected in 75% of the patients tested. According to the CIC isotype, the IgG CIC positives (75%) prevailed over IgA CIC positives (50 %).CONCLUSION:The altered production of IL-6, IL-12 and IL-10, the increased apoptosis as well as the elevated levels of CIC could be a reason for the persisting immune inflammation in TAO.

The assessment of the soluble immune complexes (IC) in human sera is traditionally performed by the C1q binding assay. In the present study, a novel method for the quantity of immune complexes was reported. The methodology was based on measuring their deposition on solid-phase C3 binding glycoprotein (CIF), using an enzyme-linked immunosorbent assay. We also used ELISA that employed anti-C3 antibodies to determined the quantity of immune complexes. The three assays were evaluated for their performance characteristics on the same specially prepared samples: 55 normal sera, 99 sera from RA, 88 sera from SLE, and 27 sera from PSS. The results were compared by reference to a common standard-heat aggregated IgG that possesses many activities of immune complexes. Three of the tests used displayed almost the same specificity (over 95%), while their relative sensitivity varied depending on the disease sera tested. The sensitivity of the assays used was recorded highest for C1q ELISA-28.97% of positive sera, followed by CIF-ELISA-19.63% and lowest for anti-C3 ELISA-17.29%. A well-expressed correlation was found between CIF-ELISA and anti-C3 ELISA data (r=0.42), and a week correlation was noted when comparing CIF-ELISA and C1q ELISA IC levels detected (r=0.28). When the correlation coefficients were calculated individually for each disease category, they were clearly different, and that reflected indirectly in different sensitivities of the test for various disease categories. We also found that the results from the simultaneous performance of the tests demonstrated low percentage positive results when three or two assays were used. This is most probably due to the different assay abilities to detect IC with different sizes and composition, which shows that a small part of IC in the tested sera can be detected simultaneously by more than one assay. On the basis of the results obtained, we concluded that optimal screening for IC could be achieved by parallel application of several different methods.