Systemic liberation of interleukin-1 beta and interleukin-1 receptor antagonist in the perioperative phase of liver transplantation

We measured systemic serum levels of interleukin-1 receptor antagonist (IL-1ra), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) during the preoperative, anhepatic, and postreperfusional phases up to the 7th postoperative day in 60 patients undergoing orthotopic liver transplantation (LTx). In contrast to IL-1 beta, IL-1ra, TNF-alpha, and IL-6 showed a significant elevation in relation to the early phase after reperfusion, while TNF-alpha displayed a high grade of scatter. In addition, IL-1ra levels were significantly elevated during the anhepatic phase. Maximum serum levels were found at 15 min after reperfusion, 120 min after reperfusion, and on the 1st postoperative day, respectively. Serum levels decreased considerably at 24 h and 7 days after reperfusion. The comparative monitoring of systemic cytokine and cytokine antagonist levels, in particular the liberation of IL-1ra and IL-6 may provide useful parameters for the development of new liver preservation theories for LTx.     

Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of schizophrenic patients

Some evidence points towards a possible autoimmune role in the aetiology of schizophrenia. Experimental findings provide contradictory results regarding abnormalities in cytokine production in this disorder. In the present study we tested the production of cytokines in CSF and serum in 16 schizophrenic patients and 10 healthy controls (tumor necrosis factor alpha - TNF alpha; interleukins IL-1 beta, IL-2, IL-6, soluble IL-2 receptor). Cytokine levels were evaluated by radioactively-labeled antibodies (IL-1 beta, IL-2, IL-6), by enzyme-linked immunoassay (TNF) and by a sandwich enzyme immunoassay (soluble IL-2 receptor). No significant differences were found in either CSF fluid or serum levels of TNF and IL-2 or IL-6. Interleukin-1 beta was significantly decreased in patients' CSF and serum as compared to controls. Soluble interleukin-2 receptor levels were decreased in CSF of patients, but highly increased in their serum in comparison with controls. Changes in various cytokine levels in CSF fluid and serum of schizophrenic patients probably reflect interrelated process of growth, degeneration or neuroimmunological abnormalities, which may all play a role in the pathophysiology of schizophrenia. The present study supports evidence for change in immune activation, probably of peripheral origin, in schizophrenic patients.     

Alterations in tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 production by natural killer cell-enriched peripheral blood mononuclear cells in chronic alcoholism: relationship with liver disease and ethanol intake

No previous studies have been reported on human alcoholism in which the pattern of cytokine secretion by natural killer (NK) cells is explored. The goal of the present study was to evaluate the role of NK cells in the production of cytokines in patients with chronic alcoholism, analyzing at the same time the possible relationship between cytokine production and both alcoholic liver disease and ethanol (EtOH) intake. A total of 30 chronic alcoholic patients-11 without liver disease [alcoholics without liver disease (AWLD) group] and 19 diagnosed of alcoholic liver cirrhosis-were included in this study. Twenty-five age- and sex-matched healthy volunteers were analyzed as controls. Production of interferon (IFN)-gamma, tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-6 was performed on NK-enriched peripheral blood mononuclear cells (PBMC) after stimulation with IL-2 and IFN-alpha. In AWLD patients, the production of TNF-alpha was significantly reduced, compared with normal controls, under both IFN-alpha (p < 0.01) and IL-2 (p < 0.05) stimulation. In patients with cirrhosis, TNF-alpha production by PBMC enriched in NK cells varied depending on the EtOH intake status at the moment of evaluation. Accordingly, an increased concentration of this cytokine was detected in the supernatants of cirrhotic patients and active EtOH intake, particularly after IFN-alpha stimulation (p < 0.05); whereas, in patients with at least 1 year of alcohol withdrawal, TNF-alpha levels remained within normal range. The results on the production of IL-6 and IFN-gamma in AWLD and cirrhotic patients showed that only cirrhotic patients with a prolonged EtOH withdrawal period display abnormal production. Accordingly, in this group of patients, a significantly increased release of IL-6 was observed after both IFN-alpha and IL-2 stimulation (p < 0.01 and p < 0.05, respectively). By contrast, a lower IFN-gamma production (p < 0.005) was detected with respect to the control group. Our results point to the existence of an abnormal cytokine secretion by NK cells from chronic alcoholism patients, which depend on both the existence of liver disease and the status of EtOH intake.     

Correlation of interleukin-1 beta, interleukin-6, and periodontitis

In order to understand the role of IL-1 beta and IL-6 in the periodontal tissue destruction coincident to periodontitis, we assessed the levels of these two mediators in both the gingival tissue and the serum of patients with periodontal disease and of periodontally healthy subjects. In addition, production of IL-6 by six healthy human gingival fibroblast (HGF) strains in response to IL-1 beta was also investigated. The levels of IL-1 beta and IL-6 in gingival tissues and in serum were examined by ELISA. Both mediators were observed to increase in diseased tissues of patients with adult periodontitis, and there was a positively significant relationship between both mediators and clinical assessments of periodontal destruction. Moreover, a significant correlation was also noted between levels of IL-1 beta and IL-6 in gingival tissues of periodontitis patients (r = 0.4334, p < 0.01). However, there was no significant difference in the serum levels of IL-1 beta and IL-6 between periodontitis patients and periodontally healthy controls. In fibroblast cultures, confluent monolayers of HGF were incubated with recombinant human IL-1 beta for 48 h at 37 degrees C in 5% CO2 and air. At the end of the culture period, supernatants were collected and assayed for IL-6 activity by inducing proliferation in the IL-6-dependent hybridoma cell line 7TD1. A dose-dependent stimulatory effect of IL-1 beta on IL-6 production by HGF was noted, wherein 3 strains exhibited higher IL-6 activity than the other 3. These data indicate that the levels of IL-1 beta and IL-6 in gingival tissues are closely related to the severity of periodontal disease and that the IL-1 beta and IL-6 produced in gingival tissues may not reflect these two mediators levels in serum. Moreover, IL-1 beta responsiveness of HGF in IL-6 production depends on both the concentration of IL-1 beta and cells of individual subjects. Since HGF are present in periodontal lesion, it is possible that IL-6 secretion stimulated by exposure to inflammatory cell products such as IL-1 beta may participate in the destruction of periodontal tissue in periodontitis.     

Mutations of Arabidopsis in potential transduction and response components of the phototropic signaling pathway

IL-1 plays an important role in the pathophysiologic responses to infection and inflammation, in part by mediating its own production and that of other proinflammatory cytokines. However, the relative contribution of IL-1 alpha and IL-1 beta to the inflammatory response has not been well clarified. Using IL-1 beta-deficient (IL-1 beta -/-) mice, we investigated the specific role of IL-1 beta in the in vivo and in vitro response to LPS. No differences between IL-1 beta +/+ and IL-1 beta -/- mice were observed in circulating levels for IL-1 alpha, IL-6, or TNF-alpha after the systemic administration of either a low (5 micrograms/kg) or high (5 mg/kg) dose of LPS. IL-1 beta -/- mice also had a normal response to LPS in terms of activation of the hypothalamus-pituitary-adrenal axis, hypoglycemia, serum amyloid A production, and anorexia. IL-1 beta -/- mice were normally sensitive to the lethal effect of LPS and were protected against LPS toxicity when pretreated with low-dose LPS. However, in vitro, peritoneal macrophages from IL-1 beta -/- mice stimulated with LPS produced significantly less IL-1 alpha than macrophages from IL-1 beta +/+ mice (p < 0.05). No differences in IL-6 or TNF-alpha synthesis were observed between macrophages from IL-1 beta +/+ and IL-1 beta -/- mice. In summary, our results suggest that either IL-1 beta is not essential for the in vivo systemic response to LPS or that its role can be fulfilled by other cytokines with overlapping activities.     

Monocyte cytokine production in an elderly population: effect of age and inflammation

OBJECTIVE: To determine the association among aging, inflammation, and cytokine production by peripheral blood mononuclear cells. POPULATION AND METHODS: We examined production of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-1 receptor antagonist (IL-1Ra), and IL-6 in 711 elderly participants in the Framingham Heart Study (mean age, 79 y) and 21 young healthy volunteers (mean age, 39 y). The elderly subjects were categorized by serum C-reactive protein (CRP) concentration, a marker of systemic inflammation. RESULTS: Production of IL-6 (p < .00001) and IL-1Ra (p < .00001) was higher in the elderly subjects than in the control group. IL-6 production increased with increasing CRP, whereas IL-1RA was uniformly elevated in elderly subjects regardless of CRP. However, we found no difference in the production of IL-1 beta or TNF-alpha between the young and elderly groups, regardless of CRP status. IL-6 population correlated with IL-1 beta (r = .36, p < .0001) and TNF-alpha production (r = .25, p < .0001), but IL-1Ra production did not. CONCLUSION: Production of IL-6 and IL-1Ra--but not IL-1 beta or TNF-alpha--was increased in the elderly compared to healthy, young subjects. The increase in IL-6 also correlated with increased production of CRP, a marker of inflammation. However, IL-1Ra was increased in the elderly independently of CRP production. Although limited by the small control group, these data suggest that dysregulation of some inflammatory cytokines occurs with age, but the role of inflammation in aging remains unclear.     

Vascular endothelial cell expression of ICAM-1 and VCAM-1 at the onset of eliciting contact hypersensitivity in mice: evidence for a dominant role of TNF-alpha

We have studied vascular endothelial activation and increased expression of ICAM-1 and VCAM-1 at the onset of the elicitation phase of oxazolone contact hypersensitivity in mice. By measuring the local uptake of i.v. administered radiolabeled anti-ICAM-1 and anti-VCAM-1 mAb, we found that endothelial ICAM-1 and VCAM-1 was increased by 4 h after challenge, 2 h later than the first peak of ear swelling and 125I-labeled human serum albumen uptake. Increased expression of endothelial ICAM-1 and VCAM-1 was significantly greater in sensitized animals than in naive animals. Anti-TNF-alpha antiserum significantly inhibited both the increase in ear thickness (p < 0.01), and the up-regulation of ICAM-1 and VCAM-1 expression (p < 0.01 for both) at 4 h. In contrast, the combination of anti-IL-1alpha and IL-1beta had only a small inhibitory effect on ICAM-1 expression (p < 0.05) and no significant effect on increased ear thickness or on VCAM-1 expression. A mixture of anti-TNF-alpha, anti-IL-1alpha, and IL-1beta was no more inhibitory for endothelial ICAM-1 and VCAM-1 expression than anti-TNF-alpha alone. ICAM-1 and VCAM-1 expression at 4 h was unaffected by a combination of mAb against alpha4 and beta2 integrins, whereas expression at 24 h was significantly inhibited (p < 0.05), suggesting that the release of TNF-alpha and other cytokines involved in the initiation of the response may not require leukocyte traffic or other leukocyte functions involving these integrins. We conclude that the early up-regulation of endothelial ICAM-1 and VCAM-1 during the elicitation of contact hypersensitivity is primarily due to the immune-dependent local release of TNF-alpha.     

The role of interleukin-8 and other cytokines in the pathogenesis of Felty's syndrome

OBJECTIVE: Felty's syndrome (FS) is defined as rheumatoid arthritis (RA) with neutropenia and, in some cases, splenomegaly; the outcome is primarily determined by the risk of infection, which is related to the degree of neutropenia. We analysed whether the clinical manifestations of FS, especially neutropenia, could be explained by abnormalities in cytokine production. METHODS: We examined the production in FS of five cytokines involved in the maturation and activation of polymorphonuclear cells (PMNs): IL-1 beta, TNF alpha, IL-8, G-CSF and GM-CSF. Because of the role of systemic IL-8 in neutrophil migration, serum IL-8 levels were also evaluated. RESULTS: Spontaneous and anti-CD16 stimulated cytokine production was similar in FS, RA and healthy controls (NC). However, anti-CD3 stimulated IL-8 production was significantly increased compared to NC in both RA and FS. FS patients who spontaneously produced G-CSF in culture were protected from bacterial infections. Serum IL-8 levels were elevated in FS and RA compared to NC (p < 0.001 for both groups). In FS, serum IL-8 was higher in patients with a history of bacterial infections compared to those without (p < 0.01) and there was a weak inverse correlation between neutropenia and serum IL-8 levels (Kendal's tau B = -0.31, p = 0.05). CONCLUSION: The neutropenia of FS cannot be explained by changes in peripheral blood cytokine production, although changes in the bone marrow microenvironment cannot be excluded. Our data do suggest a possible role for G-CSF and IL-8 in the development of certain FS complications.     

In vitro effects of diacerhein and rhein on interleukin 1 and tumor necrosis factor-alpha systems in human osteoarthritic synovium and chondrocytes

OBJECTIVE: To evaluate the in vitro effects of diacerhein, a new drug for the treatment of osteoarthritis (OA), and its active metabolite, rhein, on interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) synthesis and expression in human OA synovial membrane, and on the IL-1beta and TNF-alpha receptors on human OA chondrocytes. METHODS: Levels of IL-1beta and TNF-alpha were determined using specific ELISA in culture medium of human synovial membrane explants incubated in the presence of 1 microg/ml of lipopolysaccharide with or without therapeutic concentrations of diacerhein (1.4, 2.7, 5.4 x 10(-5) M) and rhein (1.7, 3.5, 7.0 x 10(-5) M). IL-1beta mRNA level was quantitated by Northern blotting. Using radioligand binding experiments, we determined the effects of these agents on the density and affinity of chondrocyte IL-1 and TNF receptors. RESULTS: IL-1beta synthesis was significantly inhibited by diacerhein and rhein, with maximum inhibition at 5.4 x 10(-5) M for diacerhein (p < 0.02) and 3.5 x 10(-5) M for rhein (p < 0.05). The effect of both agents on IL-1beta was found to be translational and/or post-translational, judging by the absence of effect on gene expression level. Both agents produced dose and time dependent decreases in the number of IL-1 receptors (IL-1R) on OA chondrocytes. This effect was mediated through a reduction in the level of the type I IL-1R as shown by experiments using a blocking monoclonal antibody against this receptor type. Both agents also markedly reduced the IL-1 induced synthesis and expression of stromelysin 1. Neither diacerhein nor rhein significantly affected the level of synthesis of TNF-alpha or the level of TNF-R. CONCLUSION: Diacerhein and rhein can effectively inhibit the synthesis of IL-1beta on human OA synovium, as well as the action of this cytokine at the cartilage level, by reducing the number of chondrocyte IL-1R. The effects of these agents seemed "selective" to the IL-1 system.     

Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured preoperatively in 24 patients with colorectal cancer. IL-1 beta was not elevated, IL-6 and IL-8 were markedly elevated, and GM-CSF was slightly elevated. TNF-alpha was not detected in most patients. Serum IL-6 levels correlated closely with serum IL-8 levels and with serum carbohydrate antigen (CA) 19-9 levels. Serum IL-6 levels were significantly higher in patients whose tumors exceeding 5.0 cm in diameter or spreading circumferentially. Serum IL-8 levels showed significant differences according to histological type, being lower in well differentiated adenocarcinoma compared to other types. Serum levels of IL-6 and IL-8 were significantly higher in patients with liver metastasis than in those without liver metastasis and serum levels of both these cytokines were also significantly higher in patients with lung metastasis than in those without lung metastasis. These results suggest that IL-6 and IL-8 may play an important role in the hematogenous metastasis of colorectal cancer.     

The effects of increasing exchange volume and frequency on peritoneal dialysis adequacy

We investigated serum level of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) using an enzyme-linked immunosorbent assay (ELISA) in 59 patients with systemic lupus erythematosus (SLE) and 16 healthy controls. We examined a possible association between serum levels of these cytokines and SLE activity, as well as correlation between IFN-gamma concentration and the level of TNF-alpha and IL-6 and also IL-6 and TNF-alpha. TNF-alpha and IL-6 were detectable in all 59 patients and normal individuals and their level was significantly higher in SLE patients than in the control group (p < 0.001 and p < 0.02, respectively). In contrast IFN-gamma was detectable in 23 (39%) patients and in only 3 (20%) healthy individuals. We found positive correlation between serum concentration of TNF-alpha and IL-6 with SLE activity and no such correlation with IFN-gamma. We also observed positive correlation between serum levels of IFN-gamma and TNF-alpha, IFN-gamma and IL-6 as well as TNF-alpha and IL-6. In conclusion, an increase in the serum levels of TNF-alpha and IL-6 may be useful markers for SLE activity.     

Lipopolysaccharide and its analog antagonists display differential serum factor dependencies for induction of cytokine genes in murine macrophages

Monocytes/macrophages play a central role in mediating the effects of lipopolysaccharide (LPS) derived from gram-negative bacteria by the production of proinflammatory mediators. Recently, it was shown that the expression of cytokine genes for tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interferon-inducible protein-10 (IP-10) by murine macrophages in response to low concentrations of LPS is entirely CD14 dependent. In this report, we show that murine macrophages respond to low concentrations of LPS (相似文献   

Mg2+ coordination in catalytic sites of F1-ATPase

Cytokines are hormone-like proteins which mediate and regulate inflammatory and immune responses. The purpose of this study was to investigate the effect of lipopolysaccharide (LPS) and inflammatory cytokines on regulation of interleukin-6 (IL-6) production by human gingival fibroblasts (HGF). The HGF cell lines used in this study, H-CL and F-CL, were established by the explant technique from healthy gingival tissue. Cultured cells were grown to confluency and incubated with various concentrations of LPS from Escherichia coli or Porphyromonas gingivalis or with the recombinant human cytokine tumor necrosis factor alpha (TNF-alpha), IL-1alpha, or IL-1beta. Culture supernatants were collected at various times and assessed for IL-6 production by enzyme-linked immunosorbent assay. Total RNA was isolated from the harvested cells and used to assess levels of IL-6 mRNA by the RNase protection assay. Both LPS preparations induced IL-6 production (1 to 4 ng of IL-6 per ml) by both HGF cell lines. Although TNF-alpha stimulated IL-6 production by HGF, > 10-fold-larger amounts were induced with IL-1alpha and IL-1beta. Furthermore, the addition of both IL-1alpha and TNF-alpha to cultured cells resulted in approximately 600- to 800-fold-higher levels of IL-6 than seen in control cultures, suggesting that these cytokines synergistically induced IL-6 production by HGF. IL-6 message in cultured cells was upregulated 20-fold by TNF-alpha, 1,000-fold by IL-1alpha and IL-1beta, and 1,400-fold by IL-1alpha plus TNF-alpha. IL-1alpha and TNF-alpha alone upregulate IL-6 production in a dose- and time-dependent fashion. The addition of IL-1alpha and TNF-alpha to cultured HGF cells resulted in a synergistic induction of IL-6 after 8 h of incubation and when greater than 10 pg of this combination per ml was used. Our studies show that inflammatory cytokines are hundreds of times more potent than LPS in stimulating IL-6 production by HGF.     

Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure

Idiopathic pulmonary fibrosis (IPF) and asbestosis are fibrotic interstitial lung diseases characterized by alveolar wall fibrosis with accumulation of extracellular matrix, interstitial remodeling, and increased numbers of activated alveolar macrophages. Animal models and in vitro studies have shown that macrophage cytokines, namely IL-1 beta and TNF-alpha, play significant roles in the development of fibrosis. We found significant increases for TNF-alpha release in both diseases (p < 0.01) and a significant increase for IL-1 beta release in asbestosis compared to normal controls (p < 0.01). Also, the mRNA expression of these cytokines was increased in alveolar macrophages from patients with IPF or asbestosis compared with normals. The level of TNF-alpha release in macrophage supernatants correlated with the number of neutrophils per milliliter bronchoalveolar lavage fluid returned. Chrysotile, crocidolite, amosite asbestos, and silica stimulated IL-1 beta and TNF-alpha release and up-regulated their respective mRNA in macrophages or monocytes. To evaluate the role of IL-1 beta and TNF-alpha in the accumulation of extracellular matrix, we studied collagen types I and III and fibronectin gene expression in human diploid lung fibroblasts after short term (2 h) serum-free exposure to recombinant cytokines. Both cytokines up-regulated these genes 1.5- to 3.6-fold. These cytokines have the potential to influence the remodeling and fibrosis observed in the lower respiratory tract in IPF and asbestosis.     

In vivo expression of interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, tumour necrosis factor-alpha and interferon-gamma in the fetal murine thymus

Cytokines are known to play a role in T-cell lymphopoiesis as potent growth or differentiation factors, but many experiments focusing on their role in the thymus have been conducted only in vitro. We have thus used frozen sections obtained from fetal thymuses of normal C57BL 6 mice to investigate by immunohistochemistry the presence of interleukin-1 beta (I4-1 beta), IL-2. IL-4. IL-6. interferon-7 (IFN-7) and tumour necrosis facor-alpha (TNF-alpha). The results reveal that apart from IL-2, which was not detected, all these cytokines display a time-dependent expression pattern in the normal fetal thymus. First, production of IL-4, IL-6 and TNF-alpha is detected around days 13 14; this is followed by a second wave on days 16 17, with a production of IL-1 beta, IL-4 and IL-6, and finally, just before birth (day 19), by a third wave of IL-1 beta, IL-4, IL-6, IFN-7 and TNF-alpha production. This supports the hypothesis that cytokines play a rote in T-cell lymphopoiesis.     

Increased circulating cytokine receptors and ex vivo interleukin-1 receptor antagonist and interleukin-1beta production but decreased tumour necrosis factor-alpha production after a 5-km run

BACKGROUND: The purpose of this study was to examine the effect of a 5-km run on blood leucocytes, acute-phase proteins and cytokines. In addition, cytokines were measured in the supernatants from whole-blood cell cultures incubated with lipolysaccharide (LPS). METHODS: Ten healthy, recreational trained, athletes (three women, seven men) volunteered for this investigation. Samples were drawn just before, immediately after and at 3 h, at 24 h and at 48 h after the race. RESULTS: Exercise induced a transient leucocytosis (P = 0. 0002) and a mild acute-phase reaction with increase in plasma C-reactive protein (CRP) (P = 0.0115) but not in serum amyloid A (SAA) concentrations. Although plasma interleukin 6 (IL-6) was undetectable and soluble interleukin-1 receptor type II (IL-1sRII) remained unchanged, interleukin-1 receptor antagonist (IL-1ra) concentrations were elevated directly after the race with a further increase at 3 h (P < 0.0001). Soluble tumour necrosis factor (TNF) receptors were increased immediately after the run, but the effect was more marked for sTNFr p55 (two-fold increase; P < 0.0001) than for sTNFr p75 (1.16-fold increase; P = 00007). In cell cultures, the LPS-induced release of the inflammatory cytokines doubled for IL-1beta (P < 0.0001) and for IL-1ra (P < 0.0001). In contrast, TNF-alpha production decreased after the run, and a nadir was reached at 24 h (P < 0.0001). CONCLUSION: These results suggest that a 5-km run elicits both the production of acute-phase mediators (leucocytosis and elevation of CRP) and anti-inflammatory counter-regulation as judged by the increase in circulating concentrations of IL-1ra, sTNFr p55, and sTNFrp75 and down-regulation of LPS-stimulated TNF-alpha production.     

IL-1 in gingival crevicular fluid following closed root planing and papillary flap debridement

Interleukin (IL)-1 alpha and beta are cytokines which can mediate inflammatory, bone resorbing, and reparative effects in the periodontium, but few longitudinal data exist exploring their role following periodontal therapy. This study examined gingival crevicular fluid (GCF) concentrations of IL-1 alpha and IL-1 beta at sites with shallow sulci (SS) or inflamed moderate/advanced pockets (M/AP) before and 6 months after treatment with closed scaling/root planing (SC/RP) or papillary flap debridement (PFD), all in the same subject (n = 14 patients). No significant differences were noted in IL-1 alpha or beta concentrations (determined with two-site enzyme-linked immunosorbent assays) between SS and M/AP sites at baseline. While both therapies improved clinical parameters of periodontal disease, IL-1 alpha concentration increased significantly (p < 0.05) in M/AP-PFD sites 6 months after treatment, but were unchanged in other groups. IL-1 beta concentrations were numerically lower after therapy, except for a significant increase (p < 0.05) in M/AP-PFD sites. These data suggest that surgical wound healing in an inflamed, plaque-infected site (M/AP-PFD) results in prolonged production of IL-1, which may be a reflection of the extent of tissue trauma and delayed wound healing. In spite of increased IL-1 levels, these sites demonstrated significant short-term improvement in clinical attachment level (+ 1.8 mm, p < or = 0.001) postoperatively.     

Interleukin-10, interferon gamma, interleukin-2, and soluble interleukin-2 receptor alpha detected during peritonitis in the dialysate and serum of patients on continuous ambulatory peritoneal dialysis

OBJECTIVE: To analyze interleukin (IL)-10, interferon gamma (IFN-gamma), IL-2, and soluble IL-2 receptor alpha (sIL-2R alpha) in the dialysate and serum of patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN AND PATIENTS: Samples from dialysate bags were collected during the initial month of dialysis. During peritonitis, samples were collected from the first three bags on the day of admittance to the hospital and from the night bags on days 3 and 10. Serum samples were drawn on days 1 and 10. RESULTS: IL-10 was detected in all dialysate samples except one on the first day of infection, with a peak median level of 50 pg/mL and a slow decrease thereafter. In serum the median levels never exceeded detectable levels. Patients infected with Escherichia coli or Staphylococcus aureus had higher IL-10 levels in dialysate on day 3 as compared to the remaining patients (p < 0.05). If the catheter had to be drawn, because of persistent cloudy dialysate, the IL-10 levels remained elevated for a longer time (p < 0.05). IFN-gamma and IL-2 were detected only in the dialysate of patients infected with either S. aureus or S. epidermidis. Only one serum sample showed increased IFN-gamma. SIL-2R alpha was found in all the serum and dialysis samples from the first day of infection. Contrary to the analyzed cytokines, the receptor showed severalfold higher levels in serum as compared to the dialysate. During the infection the receptor levels in the dialysate increased, while they remained stationary in the serum, indicating a local production. CONCLUSION: This is the first time IL-10 has been demonstrated in the dialysate during peritonitis in CAPD patients. In view of its role as a suppressor of the immune and inflammatory responses, it is a potentially important observation, which might have clinical implications in the future.