Arteriovenous fistula of the jugular vein: detection and follow-up with color-coded duplex ultrasound]

Increased levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have been reported in various diseases, including lung cancer. The role of the soluble form of the IL-6 receptor (sIL-6R) remains to be explored. We therefore measured IL-6, IL-8 and sIL-6R in effusion fluid and blood serum of 10 lung cancer patients with carcinomatous pleurisy (5 men, 5 women, age 64.3 +/- 4.4 years) by enzyme-linked immunosorbent assays. Serum levels of healthy individuals served as control. Concentrations of sIL-6R were much higher in serum compared to pleural effusion fluids of tumor patients (25,698 +/- 1,993 vs. 9,438 +/- 1,407 pg/ml: p < 0.0001). In contrast, IL-6 and IL-8 were found at high concentrations in carcinomatous pleural effusions in comparison to serum (IL-6: 964 +/- 176 vs. 10.2 +/- 1.3 pg/ml, p < 0.0001; IL-8: 319 +/- 85 vs. 9.6 +/- 9.6 pg/ml, p < 0.0001). The serum concentrations of IL-6 were not significantly increased in lung cancer patients (10.2 +/- 1.3 pg/ml) in comparison to controls (7.3 +/- 1.0 pg/ml). IL-8 was detected in the serum of only 1 patient and in low levels in the serum of controls (8.0 +/- 1.5 pg/ml; all values are mean +/- SEM). We conclude from this study that decreased levels of sIL-6R, but increased levels of IL-6 and IL-8, are found in pleural effusion fluid of patients with lung cancer and carcinomatous pleurisy. The low sIL-6R levels in the presence of high IL-6 levels in pleural effusions and the high sIL-6R levels in the presence of low IL-6 levels in serum may suggest a downregulation of sIL-6R expression of sIL-6R shedding in the presence of excessive amounts of IL-6.     

Soluble cytokine receptors and receptor antagonists are sequentially released after trauma

Cytokine receptors and receptor antagonists (RAs) have been identified in trauma patients. We hypothesized that after traumatic injury, a sequential release of soluble cytokine receptors and RAs may exist that mirrors the release of the primary cytokines themselves. Twenty-two patients were included in the study: 14 males and 8 females. The mean age was 30.1 +/- 12.5 (range, 19 to 71), and the mean Injury Severity Score was 28.7 +/- 12.6 (range, 4 to 57). There were 15 survivors and 7 nonsurvivors. Samples were collected on arrival to the emergency department and at serial intervals for up to 7 days. Monoclonal antibody enzyme-linked immunosorbent assay kits to tumor necrosis factor (TNF), soluble TNF-receptor (sTNF-R) 55 kd and 75 kd, interleukin (IL)-1 and IL-1 RA, and IL-2 and IL-2r were used. Sera from 22 healthy individuals were used as normal controls. No TNF, IL-1, or IL-2 could be detected in any patient sera after injury. Control levels for the soluble cytokine receptors and RAs were as follows: sTNF-R 55 kd, 607 +/- 89 pg/mL; sTNF-R 75 kd, 2,141 +/- 169 pg/mL; IL-1 RA, 291 +/- 35 pg/mL; and IL-2r, 426 +/- 53 U/mL. In trauma patients, both 55 kd and 75 kd sTNF-R were significantly elevated on arrival to the emergency department, with values of 2,441 +/- 506 pg/mL (p < 0.001) and 4,736 +/- 537 pg/mL (p < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Keratosis follicularis spinulosa decalvans: report of a new pedigree

Soluble interleukin-6 receptor (sIL-6R) has previously been shown to potentiate the activity of interleukin (IL)-6, which may display antitumor activity. We evaluated sIL-6R and IL-6 levels in the sera of 24 patients following transplantation (allogeneic, n=17; autologous, n=7). Five patients developed acute graft-versus-host disease (AGVHD), three had early graft rejection, and three had an early relapse following bone marrow transplantation (BMT). Soluble IL-6R levels were evaluated at day - 10, day 0, day of engraftment, and during BMT-related complications, using IL-6R-specific monoclonal antibodies (mAb) and double-sandwich ELISA. In normal controls, sIL-6R and IL-6 levels were 20+/-3 ng/ml and 0.01+/-0.005 ng/ml, respectively. Soluble IL-6R levels increased in direct correlation with engraftment in the uneventful allogeneic transplants (17.7+/-2.1 ng/ml at day 0 to 49.7+/-2.6 ng/ml at day of engraftment, n=6, P<0.05) as well as in the autologous transplants (26.8+/-2.82 at day 0 to 66.4+/-12.9 at day of engraftment, n=5, P=0.01). In contrast, IL-6 levels declined with time during the conditioning period and showed only a modest elevation following BMT. Increased levels of sIL-6R and IL-6 were found in the patients who developed AGVHD (23.8+/-4.2 and 0+/-0 ng/ml at day 0 to 79+/-6.9 and 0.26+/-0.04 ng/ml, respectively, at time of AGVHD, n=5, P=0.01). No correlation was found between the severity of AGVHD and sIL-6R levels. In the three patients with early relapse, sIL-6R levels increased from 30+/-0 ng/ml at day 0 to 90 ng/ml (P=0.05) and IL-6 levels increased from 0 to 0.16+/-0 ng/ml, respectively. The mean elevation of sIL-6R in the patients with early relapse and AGVHD was significantly higher than the mean elevation in the patients with the relatively smooth engraftment (P<0.05). Contrary to these findings, in the three patients with graft rejection, sIL-6R levels decreased while IL-6 was found to be elevated. Basic disease, conditioning regimen, type of transplant, GVHD propylaxis, and T cell depletion had no effect on sIL-6R or IL-6 levels. In summary, sIL-6R levels positively correlated with engraftment. Both sIL-6R and IL-6 levels were found to be significantly elevated in patients who developed AGVHD or early relapse following BMT. Therefore, the sIL-6R level may be used as a tool for assessing engraftment and transplant-related complications following BMT.     

Serum levels of interleukin 1 and tumor necrosis factor alpha correlate with peritoneal adhesion grades in humans after major abdominal surgery

Peritoneal adhesions are a leading cause of potential morbidity and mortality. We undertook this prospective study to determine the clinical relevance of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) levels as biological markers for peritoneal adhesion formation in humans. Fifteen patients who had previous colectomies and were undergoing re-exploration for an elective vascular procedure were studied. Blood samples were collected from each patient preoperatively and 30 minutes after the abdominal incision was made. Serum levels of IL-1 and TNF-alpha were determined using enzyme-linked immunosorbent assay kits. Adhesions were graded using an adhesion scale of 0 (none), 1 (mild), 2 (moderate), and 3 (extensive, dense). Preoperative levels of IL-1 and TNF-alpha did not differ significantly among all patients (IL-1 level was 60 +/- 14 pg/mL, and TNF-alpha level was 45 +/- 11 pg/mL; mean +/- standard deviation). Significant correlation was observed between grades of adhesions and early intraoperative levels of IL-1 [101 +/- 36 pg/mL for grade 1 (n = 8) vs 298 +/- 73 pg/mL for grade 3 (n = 6); P < 0.01] and TNF-alpha (88 +/- 23 pg/mL for grade 1 vs 261 +/- 88 mL for grade 3; P < 0.02). We conclude that early elevations of IL-1 and TNF-alpha are reliable biological markers for postoperative adhesions in humans. Studies utilizing cytokines antibodies to these markers may further elucidate the efficacy of this method for prevention of peritoneal adhesions.     

The Stomatology Information Retrieval (Reference) System]

BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by monoclonal proliferation of activated Langerhans cells. Neither etiology nor pathomechanism of this disorder is presently known. However, despite monoclonality LCH might represent a reactive clonal disorder induced by immune dysfunction rather than a malignant process. To investigate a putative cytokine dysregulation in the pathogenesis of this disorder and searching for parameters of both disease activity and prognosis, serum concentrations of proinflammatory and T-cell derived cytokines were evaluated in LCH patients. MATERIALS AND METHODS: Serum levels of IL-1 beta, IL-2, sIL-2R and TNF-alpha were determined by ELISA in seven children with different types of LCH: Three children (aged 6, 10 and 14 years, respectively) with single system/single bone disease; one child (11 years) with recurrent single system/multiple bone disease and three children (1, 2 and 2 years, respectively) with multisystem disease. RESULTS: sIL-2R was elevated at diagnosis in seven children as compared to healthy adults (mean +/- SEM: 5,256 +/- 3,751 U/ml vs. 73 +/- 5.5 U/ml; P < 0.005) or healthy children (mean +/- SEM: 10,195 +/- 2,798 pg/ml vs. 2,638 +/- 156 pg/ml; P < 0.01). A positive correlation between serum levels of sIL-2R and extent of the disease could be observed. During remission, sIL-2R levels declined. IL-1 beta, IL-2, and TNF-alpha remained within the normal range during the study period. CONCLUSIONS: Elevated sIL-2R levels seem to correlate positively with both extent and activity of LCH, thus indicating a pathological T-cell activation as a pathogenetic factor. sIL-2R level is a promising parameter to monitor disease activity in LCH and may also be of prognostic relevance.     

Lymphocyte activation and cytokine production in autoimmune hemolytic anaemia (AIHA)

We studied 16 patients affected by autoimmune hemolytic anaemia (AIHA), both idiopathic and associated with other diseases (B and T lymphoma, B hepatitis, gastric carcinoma, systemic lupus erythematosus) or alpha-methyldopa therapy, in order to value T- and B-cell activation. We determined the count of T- and B-cell subsets in peripheral blood, the proliferative response of peripheral blood lymphocytes (PBL) to phytohemagglutinin (PHA) and to pokeweed mitogen (PWM), the percentage of CD25+ cells in culture and interleukin (IL)-1alpha, IL-2, IL-4, tumor necrosis factor (TNF)alpha and soluble IL-2 receptor (sIL-2R) levels in sera and in culture. Except for an increase in CD4+ and CD8+ T cell number in a case of AIHA associated with a T lymphoma and an increase in the percentage of CD5+ and PCA1+ B cells in two cases of AIHA associated with B lymphoma and with SLE, no further data showed a relationship with the disease possibly associated with AIHA, so both idiopathic and secondary AIHA cases were analyzed together. CD4+ T cells were reduced in number in 9 cases, while CD8+ T cells were reduced in 6 cases. The percentage of CD5+ B cells was increased in 5 cases. The percentage of PCA1+ cells was increased in all cases (mean +/- sd: 18 +/- 22 vs 0,2 +/- 1 in controls). The average PBL proliferative response to PHA was reduced (S.I. 71 +/- 55 vs 138 +/- 45 in controls) as well as that to PWM (S.I. 27 +/- 21 vs 75 +/- 24 in controls), despite IL-2 high levels, in all cases, in both sera (mean +/- sd: 648 +/- 351 pg/ml vs 16 +/- 4 pg/ml in controls) and culture supernatants (mean +/- sd: 1045 +/- 677 pg/ml vs 195 +/- 51 pg/ml in controls). In PHA stimulated cultures the percentage of CD25+ cells was reduced (mean +/- sd: 37 +/- 18 vs 63 +/- 14 in controls), sIL-2R levels were like controls in 7 cases. In sera sIL-2R levels were increased in all cases (mean +/- sd: 1256 +/- 465 U/ml vs 256 +/- 114 U/ml in controls), IL-1alpha was increased in all cases too, while IL-4 levels were increased only in 7 cases. Linear regression analysis generally showed a low relationship between S.I. and IL-2, IL-4 and sIL-2R levels in supernatants of PHA stimulated culture as well as between S.I. and the percentage of CD25+ cells. Taken together these data suggest a state of B- and T-cell hyperactivation in AIHA. The low PBL proliferative response in vitro, explained in previous studies as a temporary functional exhaustion, might be itself a sign of the complete lymphocyte activation occurring in vivo in AIHA.     

The prognostic value of soluble interleukin-6 receptor in patients with multiple myeloma

BACKGROUND: The effect of interleukin-6 (IL-6), the major growth factor for myeloma cells, may be enhanced by soluble IL-6 receptor (sIL-6R). Therefore, the current study investigated the clinical significance of serum sIL-6R in patients with multiple myeloma (MM). METHODS: Serum levels of sIL-6R were determined by enzyme-linked immunoassay in 55 normal controls, 81 individuals with monoclonal gammopathy of undetermined significance (MGUS), and 164 patients with MM in various phases of the disease. RESULTS: sIL-6R concentrations were higher in MM patients (162.0 +/- 134.6 ng/mL) than in individuals with MGUS (58.9 +/- 36.7 ng/mL) or in controls (45.6 +/- 22.3 ng/mL) (P = 0.0000). sIL-6R was not found to have a significant linear correlation with any other parameter, including IL-6, beta2-microglobulin (beta2-m), and neopterin, either in newly diagnosed cases or during the course of the disease. In addition, there were no statistically significant differences in sIL-6R concentrations between the clinical stages at the time of diagnosis. In univariate logistic regression analysis sIL-6R was a significant but weak prognostic indicator (P = 0.000000). Kaplan-Meier analysis showed that elevated levels of sIL-6R were associated with shorter survival (P = 0.00282). Patients also were stratified according to their serum beta2-m and sIL-6R levels. Patients with low levels of both parameters had a clear survival benefit over the other groups (P = 0.000000). CONCLUSIONS: The correlation between sIL-6R levels and survival is significant but weak, making it unlikely to be of much value in predicting the outcome of patients with MM alone. The results of the current study support the role of sIL-6R levels in improving the prognostic value of beta2-m and in discriminating patients with MM from individuals with MGUS.     

In vivo platelet and T-lymphocyte activities during pulmonary tuberculosis

Platelets have been suggested to play a role in the inflammatory response, including defence against bacteria. The aims of this study were to determine in vivo platelet activity during the clinical course of pulmonary tuberculosis and to investigate whether or not there is a correlation between the magnitude of platelet activation and the extent of the pulmonary disease. T-lymphocyte activity was also analysed in the patients. Platelet factor-4 (PF4) and soluble interleukin-2 receptor-alpha (sIL-2Ralpha) concentrations were used as markers of platelet and T-lymphocyte activation, respectively. Twenty-five patients with pulmonary tuberculosis were studied. Fifteen healthy subjects served as a control group. The levels of both sIL-2Ralpha (3,000+/-1,948 pg x mL(-1)) and PF4 (103.1+/-6.7 IU x mL(-1)) were significantly higher in the patients with tuberculosis than in the control group (984+/-360 pg x mL(-1) and 78.2+/-23.9 IU x mL(-1), respectively) (Mann-Whitney U-test, p<0.001 for both comparisons). The plasma PF4 levels were found to be well correlated with the extent of pulmonary lesions on chest radiography (the Spearman's bivariate correlation analysis, r=0.65, p<0.001). However, sIL-2Ralpha concentrations did not correlate with the extent of disease. In conclusion, it has been suggested that platelet and T-lymphocyte activation occurs during pulmonary tuberculosis. The good correlation between platelet activation and the extent of pulmonary tuberculosis might be ascribed to a pathophysiological role of platelets in pulmonary tuberculosis.     

Endogenous interleukin-2 serum levels in children infected with human immunodeficiency virus

Levels of interleukin-2 (IL-2) in serum obtained from human immunodeficiency virus (HIV)-infected children at health maintenance visits were measured to characterize endogenous IL-2 responses and to examine the association between these responses and progression of immunosuppression. IL-2 was detectable (level >8.7 pg/mL) in the serum of 28 of 45 HIV-infected children; 42% (19 of 45) had serum IL-2 levels of >39 pg/mL. Children without evidence of immunosuppression (Centers for Disease Control and Prevention Pediatric HIV Classification Immunologic Category 1, n = 15) and children with severe immunosuppression (immunologic category 3, n = 20) had statistically significant lower serum IL-2 levels (mean +/- [SD], 134.4 +/- 227.3 pg/mL and 18.2 +/- 30.3 pg/mL, respectively) than those with moderate immunosuppression (mean +/- [SD], 450.5 +/- 311.8 pg/ml; immunologic category 2, n = 10) (P < .05, Wilcoxon rank sum test). In those children in whom immunosuppression was evident, decreasing serum IL-2 levels correlated with depletion of CD4+ lymphocytes (r = 0.74), whereas there was an inverse correlation between serum IL-2 levels and CD4+ lymphocyte counts (r = -0.47) in children with no or moderate immunosuppression.     

Secondary hyperparathyroidism is an expected consequence of parathyroidectomy for primary hyperparathyroidism: a prospective study

BACKGROUND: Parathyroidectomy for primary hyperparathyroidism (PHPT) can cause secondary hyperparathyroidism, with increased serum parathyroid hormone (PTH) and normal or low serum calcium concentrations. METHODS: A prospective study investigated 78 consecutive patients who underwent exploration for PHPT. Serum intact PTH and total calcium concentrations were measured the evening after operation and ionized Ca++ the following morning. These levels were reassayed 1 week later. RESULTS: Before operation, the mean PTH level was 138 +/- 15 pg/mL, total calcium concentration was 11.6 +/- 0.1 mg/dL, and ionized Ca++ concentration was 1.44 +/- 0.02 mmol/L. On the night of the operation, the PTH level was 11 +/- 2 pg/mL, and the total calcium concentration was 8.9 +/- 0.1 mg/dL. Fifty-five patients had hypoparathyroidism, with a PTH level less than 10 pg/mL. The day after the operation, the ionized Ca++ level was 1.14 +/- 0.01 mmol/L. One week later, PTH, ionized Ca++, and total serum calcium concentrations returned to normal levels. In 9 patients (12%), PTH levels were increased (98 +/- 16 pg/mL), although ionized Ca++ concentrations were normal (1.18 +/- 0.02 mmol/L), demonstrating secondary hyperparathyroidism. Risk factors for postoperative secondary hyperparathyroidism included older age, symptomatic hyperparathyroidism, higher preoperative PTH and alakaline phosphatase levels, and lower serum phosphorous levels. In 70% of these patients, PTH levels returned to normal in 3 to 12 months. CONCLUSIONS: Secondary hyperparathyroidism occurs in 12% of patients after surgical treatment of PHPT. It is transient, possibly compensating for relative hypocalcemia.     

Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is caused by the hyperactivation of T cells and macrophages. The clinical characteristics associated with this disease result from overproduction of Th1 cytokines including interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-alpha). In this study, we analyzed the production of IL-12 and IL-4, which determine Th1 and Th2 response, respectively, and IL-10, which antagonizes Th1 cytokines, in 11 patients with HLH. IL-12 was detected in plasma in all patients (mean peak value, 30.0 +/- 5.0 pg/mL), while IFN-gamma was massively produced in nine patients (mean peak value, 79.2 +/- 112.0 U/mL). IL-4 was not detected in any of the patients. Plasma IL-10 levels were elevated in all patients (mean peak value, 2,698.0 +/- 3,535.0 pg/mL). There was a positive correlation between the levels of IFN-gamma and IL-10 (P < .01). The plasma concentrations of these cytokines were initially high, before decreasing after the acute phase. However, the decrease in IL-10 levels was slower than that of IFN-gamma. Although the concentration of IL-12 was high at the acute phase, in some patients, a peak in the level was delayed until the chronic phase. Thus, in HLH, production of cytokines that promote development of Th1 cells appears to be predominant over that for Th2 cell development. Overproduction of IL-10 was also observed indicating that a mechanism suppressing hyperactivation of Th1 cells and monocytes/macrophages functions in patients with this disease.     

Detection of soluble IL-2 receptor in the serum and bone marrow of patients with minimal residual hematological malignancies: induction under therapy with IL-2

We measured the soluble IL-2 receptor alpha (sIL-2R alpha) in sera and in bone marrow of 20 patients with minimal residual hematological malignances, 6 of them with multiple myeloma (MM), 8 with Hodgkin's disease (HD) and 6 with non-Hodgkin's lymphoma (NHL), low grade. Compared to 10 normal individuals, HD and NHL group of patients had in sera significantly increased levels of sIL-2R alpha (252.8 +/- 42.9 versus 1437.2 +/- 1639 and 761.8 +/- 431 U/ml, respectively). After low-dose IL-2 given subcutaneously once daily at a dose of 1.8 x 10(6) U/patient for 3 weeks, additional significant increase in levels of IL-2R alpha was observed in sera and in bone marrow of patients with NHL (761.8 +/- 431 versus 2633 +/- 788 U/ml and 785 +/- 448 versus 2475 +/- 431 U/ml, respectively). The increase of sIL-2R alpha level after IL-2 therapy was also seen in sera and in bone marrow of HD and MM group; however, because of high standard deviation this increase was not statistically significant. We conclude that 1) in comparison to healthy subjects the levels of sIL-2R alpha remained elevated in HD and NHL patients, even at the stage of minimal residual disease (MRD) after intensive chemotherapy or radiotherapy, 2) the levels of sIL-2R alpha which appeared in sera and bone marrow of patients after IL-2 therapy seemed to be dependent on the type of hematological disorders.     

Induction of soluble IL-2 receptor in patients with myelodysplastic syndromes undergoing high-dose interleukin-3 treatment

Sera of ten healthy controls and of 15 patients with myelodysplastic syndromes (MDS) were investigated for soluble interleukin-2 receptor (sIL-2R) with a cell-free enzyme-linked immunosorbent assay (ELISA). The patients with MDS underwent treatment with IL-3: eight patients at dose levels of 250 and 500 micrograms/m2 s.c. daily for 15 days, and seven patients at the dose levels of 60 and 125 micrograms/m2 s.c. three times per week for 12 weeks. None of the patients had reported infectious episodes or been under treatment with cytotoxic drugs and/or cytokines within the preceding 2 months. sIL-2R levels were elevated in MDS patients compared with healthy controls (p < 0.001). sIL-2R increased in the high-dose treatment group from 504 +/- 68 U/ml to 731 +/- 199 U/ml (p < 0.025). The increased sIL-2R expression in MDS could be a primary event due to involvement of lymphocytes in the malignant clone or due to a secondary alteration of the cytokine network caused by chronic neutropenia. A down-regulation of the immune response caused by neutralization of free IL-2 by sIL-2R during IL-3 therapy seems possible.     

Role of interleukin 8 in the genesis of acute respiratory distress syndrome through an effect on neutrophil apoptosis

OBJECTIVE: To evaluate the role of interleukin 8 (IL-8) in the regulation of neutrophil (PMN) apoptosis in normal plasma and plasma from patients with early, fulminant acute respiratory distress syndrome (ARDS). DESIGN: Experimental study using cultured human PMNs. SETTING: University hospital, level I trauma center. PARTICIPANTS: Plasma was obtained from 6 patients with early, fulminant posttraumatic ARDS (mean Injury Severity Score, 26). All samples were drawn within 24 hours after injury. Plasma was also taken from 13 healthy control subjects. These controls were also used as sources of PMNs. MAIN OUTCOME MEASURES: Effect of early, fulminant ARDS and normal plasma on spontaneous apoptosis, CD16, and CD11-b expression in PMNs in vitro; levels of IL-8 in plasma; correlation of extracellular IL-8 concentration with rate of PMN apoptosis; and effect of IL-8 blockade on PMN apoptosis, CD16, and CD11-b expression in ARDS and normal plasma. RESULTS: Plasma from patients with early, fulminant ARDS inhibited spontaneous PMN apoptosis at 24 hours (35%+/-5% vs 54%+/-5%; P=.01). Neither CD16 nor CD1l-b differed significantly between the 2 groups. The mean plasma level of IL-8 in patients with early, fulminant ARDS was 359+/-161 pg/mL vs 3.0+/-0.4 pg/mL in healthy controls (P<.05). Interleukin 8 inhibited apoptosis in plasma-free medium at low doses (1-50 pg/mL) but had no significant effect at higher doses (100-5000 pg/mL) (P<.05). Interleukin 8 blockade with monoclonal antibody suppressed apoptosis in normal plasma (28%+/-5% with monoclonal antibody vs 51%+/-5% without monoclonal antibody; P=.008) but not in plasma from patients with early, fulminant ARDS (29%+/-5% with monoclonal antibody vs 34%+/-6% without monoclonal antibody; P=.67). It had no effect on CD16 or CD11-b expression in either plasma. CONCLUSIONS: Plasma from patients with early, fulminant ARDS contains soluble factors that inhibit PMN apoptosis in vitro. Low levels of IL-8 inhibit PMN apoptosis in normal plasma. Although plasma levels of IL-8 are markedly elevated in early, fulminant ARDS, IL-8 is not directly responsible for the antiapoptotic effect of plasma from patients with early, fulminant ARDS.     

IL-6 and soluble IL-6 receptor levels change differently after surgery both in the blood and in the operative field

To investigate alterations in post-operative levels of IL-6 and soluble IL-6 receptor (sIL-6R), we examined their levels in serum and samples of drainage fluids from 26 patients who underwent thoracoabdominal surgery. Serum IL-6 levels reached the maximum within the first post-operative day and decreased thereafter. The IL-6 levels in the drainage fluid were much higher than in the serum (458 +/- 101-fold; mean +/- SEM) in the early post-operative phase. A large quantity of sIL-6R levels was present in blood samples. The time course of serum sIL-6R levels in 26 patients showed no significant change. sIL-6R concentrations in the drainage fluid were significantly lower than in serum (4.5 +/- 1.1-fold; mean +/- SEM) in the early post-operative phase. We propose that IL-6 is produced in the operative field and enters the peripheral blood stream to induce elevation of serum IL-6. On the other hand, sIL-6R levels in the operative field are lower than in the serum, and the serum sIL-6R levels are not influenced by surgical trauma. These data suggest that sIL-6R is being constantly produced in areas other than the operative field, while sIL-6R level is reduced by consumption in the operative field. Mechanisms to cope with surgical stress, involving sIL-6R together with its ligand IL-6 may thus exist.     

Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive non-Hodgkin's lymphoma

We investigated the prognostic significance of interleukin-10 (IL-10) and soluble interleukin-2 receptor (sIL-2r) levels in the pretreatment serum of 105 individuals with newly-diagnosed aggressive non-Hodgkin's lymphoma (NHL). Commercially available enzyme-linked immunoassay kits were used for cytokine and receptor measurements. Detectable levels of IL-10 were found in 42 (40%) patients at diagnosis, with no correlation with clinico-haematological parameters, but in no control samples (P < 0.001). Pretreatment concentrations of sIL-2r were markedly increased in individuals with NHL when compared to controls (2614 +/- 893 U/ml v 219 +/- 65 U/ml, P < 0.001), patients with stage III/IV presenting higher values than those with stage II disease (3885 +/- 1196 U/ml v 1732 +/- 646 U/ml, P < 0.001). No single parameter was associated with the achievement of complete remission, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subset of patients with a high probability of failing induction therapy (P < 0.001). Life-table analysis also indicated that patients with these characteristics have a significantly shorter event-free survival. In a multivariate analysis the combination of IL-10 with sIL-2r was found to have greater predictive strength than the combination of IL-10 with beta 2-microglobulin. We conclude that IL-10 and sIL-2r measurements can be expected to improve existing methods of risk assignment in aggressive NHL.     

The role of cytokines in Henoch Schonlein purpura

Serum levels of tumor necrosis factor (TNF) and interleukin(IL-1) were studied in 20 HSP patients, in the acute phase and after remission, by ELISA technique. Skin biopsies obtained during the acute phase both from a lesion and from unaffected skin, as well as during remission, were immunostained for TNF, IL-1, and IL-6. The mean age of the patients was 9.8 (5-13). Mean serum TNF levels during the acute phase and remission were 14.0 +/- 8.9 pg/ml, and 6.8 +/- 2.4 pg/ml, respectively (p < 0.05). Serum TNF levels in patients with renal involvement (18.8 +/- 10.2 pg/ml) were significantly higher than in those without (10.8 +/- 6.5 pg/ml) (p < 0.05). Serum levels of IL-1 in the acute phase and remission were undetectable. All specimens showed leukocytoclastic vasculitis. Immunohistochemical studies revealed TNF, and a less intense IL-1 and IL-6 staining in the nucleated epidermal layer, with a granular, intracellular pattern. Staining was significantly increased in the affected skin during the acute phase. These results suggest that TNF, IL-1, and IL-6 may play a role as a mediator of inflammation in HSP.     

Region of birth and black diets: the Harlem Household Survey

Human obesity is associated with an increased tumor necrosis factor-alpha (TNF-alpha) mRNA expression in adipose tissue. TNF-alpha decreases insulin-dependent glucose uptake by inhibiting autophosphorylation of the insulin receptor, suggesting that TNF-alpha may play a role in insulin resistance. In this study, we analyzed plasma levels of TNF-alpha in 40 70-year-old men with newly detected non-insulin-dependent diabetes mellitus and in 20 age-matched controls. Twenty of the patients had a moderate level of insulin resistance and 20 were severely insulin resistant. The plasma levels of TNF-alpha were higher in patients (4.00+/-1.53 pg/mL in moderately insulin resistant and 4.91+/-1.43 pg/mL in severely insulin resistant subjects) than in controls (3.27+/-0.79 pg/mL, P<0.001). TNF-alpha was significantly related to body mass index, fasting glucose levels, and serum triglyceride levels and inversely related to the high density lipoprotein cholesterol level. The finding of an association between high plasma levels of TNF-alpha and several metabolic abnormalities characteristic for the insulin resistance syndrome suggests that TNF-alpha may be involved in the pathogenesis of non-insulin-dependent diabetes mellitus.     

High levels of interleukin-12 in the aqueous humor and vitreous of patients with uveitis

OBJECTIVE: This study aimed to investigate the role of interleukin-12 (IL-12) and interleukin-10 (IL-10) in initiation and maintenance of intraocular inflammation. DESIGN: Case series. PARTICIPANTS: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured in 22 patients with uveitis undergoing cataract surgery, paracentesis of the anterior chamber, and/or vitrectomy for diagnostic reasons, and in 4 patients with cataract only. INTERVENTION: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured with specific enzyme-linked immunosorbent assays. MAIN OUTCOME MEASURES: Disease activity was correlated to IL-12 levels in the aqueous humor and the vitreous of patients with uveitis. RESULTS: Cytokine levels found in the anterior chamber and the vitreous are presented in picogram/milliliter (medium; range). The highest IL-12 levels were found in patients with active uveitis (108.5 pg/ml; 72-293 pg/ml). Interleukin-12 in patients with moderate uveitis or with their disease in remission was lower (32 pg/ml; 15-94 pg/ml) than in patients with active disease (P > 0.001) but higher than in the control group (10.5 pg/ml; 9-14 pg/ml). Interleukin-10 was detectable in only 3 of 22 patients with uveitis (12 pg/ml; 9-23 pg/ml). CONCLUSION: The authors found statistically significant differences of IL-12 levels in the various patient groups (active vs. inactive vs. control). These results support the idea that these uveitis cases represent type 1 (Th1)-T lymphocyte-mediated diseases in which IL-12 plays a pivotal role in the initiation and maintenance of the intraocular inflammation. The high levels of IL-12 in the vitreous and/or aqueous humor of the patients with uveitis suggest that susceptibility or resistance to ocular autoimmunity may be connected to a genetic predisposition to an elevated Th1 response.     

A study of cis-diamminedichloroplatinum(II) suppositories for the treatment of rabbit uterine endometrial carcinoma

OBJECTIVE: To determine the effects of continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) on endothelin-1 (ET-1) levels in patients with end-stage renal disease (ESRD) and to assess the relationship between plasma ET-1 levels and selected patient parameters. DESIGN: Prospective, nonrandomized comparison study. SETTING: Outpatient CAPD and HD units of a university medical center. PARTICIPANTS: Twelve ESRD patients (6 on CAPD and 6 on HD) and 5 healthy normotensive subjects. INTERVENTIONS: CAPD patients had blood and peritoneal dialysate samples collected and measurements made following an overnight exchange. HD patients had blood collected and measurements made at 0 hours (basal) and again at 3 hours during a midweek HD session. Blood samples were also collected from normal subjects and served as ET-1 controls. MEASUREMENTS: ET-1 and patient parameters (creatinine, peritoneal dialysate volume, blood pressure, body weight, age, and treatment duration) were determined. Data are reported as the mean +/- one standard deviation. RESULTS: Plasma and dialysate ET-1 levels in the CAPD group were 19.5 +/- 4.2 pg/mL and 9.2 +/- 4.2 pg/mL, respectively. The control group plasma and unused dialysate contained no detectable ET-1 (< 3.0 pg/mL, the limit of detection). The peritoneal clearance of ET-1 was less than that of creatinine (2.29 +/- 0.69 mL/minute vs 4.22 +/- 0.66 mL/minute, p = 0.005). The basal (0 hour) plasma ET-1 level in the HD group (16.5 +/- 7.8 pg/mL) did not differ from that of the CAPD group, p = 0.423. Furthermore, no differences in patient parameters were detected between the CAPD and basal HD groups. Although the mean arterial pressure (MAP) decreased during HD, the plasma ET-1 level at 3 hours (13.5 +/- 5.4 pg/mL) remained unchanged from the basal level, p = 0.307. An analysis of pooled data from the CAPD and HD groups revealed no significant correlation between plasma ET-1 and MAP, body weight, creatinine, or treatment duration. There was, however, a positive correlation between plasma ET-1 and age (r = 0.643, p = 0.024).