Increased in vitro release of soluble interleukin 2 receptor by colonic lamina propria mononuclear cells in inflammatory bowel disease.

Increased concentrations of the soluble form of the interleukin 2 receptor have been observed in the sera of Crohn's disease and ulcerative colitis patients. In this study we have observed the spontaneous release of soluble interleukin 2 receptor by unstimulated, isolated normal and inflammatory bowel disease colonic lamina propria mononuclear cells. Lamina propria mononuclear cells from Crohn's disease patients (median = 204 U/ml (interquartile range 126-396, n 17) secreted significantly (p less than 0.01) more soluble interleukin 2 receptor than normal controls (median = 124.5 U/ml (108-131), n 12). No statistically significant differences were seen between ulcerative colitis (median = 135 U/ml (92-196), n 20) and normal controls. Moreover, significantly (p less than 0.01) increased amounts of soluble interleukin 2 receptor were secreted by colonic diverticulitis lamina propria mononuclear cells (median = 259 U/ml (149-282), n 15) which were used as disease specificity controls. Time course experiments showed that the majority of soluble interleukin 2 receptor was released by isolated lamina propria mononuclear cells in the first six days of culture. Upon stimulation with pokeweed mitogen, Crohn's disease (median = 2258 U/ml (1435-3584), n 14), normal control (median = 2622 U/ml (2030-3180), n 14) and diverticulitis lamina propria mononuclear cells (median = 2745 U/ml (1733-3192), n 10) reached similar maximal soluble interleukin 2 receptor secretion levels, while ulcerative colitis lamina propria mononuclear cells secreted significantly (p less than 0.005) less soluble interleukin 2 receptor (median = 912 U/ml (494-1259), n 17). These results suggest that enhanced shedding/secretion of soluble interleukin 2 receptor by intestinal lymphocytes may account in part for increased serum soluble interleukin 2 receptor concentrations during chronic intestinal inflammatory reactions.     

Mononuclear cell activation in Crohn's disease. Evaluation using serum assay of neopterin and interleukin-2 soluble receptors

To determine the degree of mononuclear blood cell activation in Crohn's disease (CD), 65 patients were prospectively investigated (22 with mild, 26 with moderate and 17 with severe disease). Serum levels of soluble receptors for interleukin-2 (SR-IL-2) were measured by ELISA. In CD patients SR-IL-2 levels were significantly higher (m = 707 +/- 326 U/ml) than in three other groups: 70 controls (m = 258 +/- 87 U/ml, p less than 0.0001); 8 patients with acute infectious colitis (m = 405 +/- 216 U/ml, p less than 0.0001); 101 HIV seropositive subjects (m = 564 +/- 216 U/ml, p less than 0.002). There was a positive correlation between SR-IL-2 level and the Van Hees activity index (r = 0.595, p less than 0.0001). On the other hand, the numbers of activated T cells (CD 3+, HLA DR+), CD 4+, CD 8+ and NK cells did not differ according to the CD activity groups. Furthermore, CD patients treated with steroids (n = 39) did not differ from those without any medication. As a marker of monocyte activation, serum neopterin level was determined by RIA. All CD patients considered as a group, serum neopterin level was 2.89 +/- 1.44 ng/l (n less than 2.5 ng/l). Neopterin level increased with disease activity (1.97 +/- 0.92 vs 3.10 +/- 1.46 vs 3.74 +/- 1.36, p less than 0.01), and was positively correlated with SR-IL-2 (r = 0.609, p less than 0.0001). These results suggest a monocyte-macrophage activation in CD, which parallels disease activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Soluble interleukin-2 receptor, interleukin-6 and interleukin-1 beta in patients with Crohn's disease and ulcerative colitis: preoperative levels and postoperative changes of serum concentrations.

Crohn's disease (CD) and ulcerative colitis (UC) show an intestinal activation of T cells and macrophages within the inflamed lesions. The aim of the present prospective study was to determine whether circulating interleukins (IL) represent useful markers of immune activation in vivo and to characterize their respective roles in monitoring disease activity. Serum concentrations of the soluble IL-2 receptor (sIL-2R), IL-6 and IL-1 beta were measured in 10 patients with CD and 10 patients with UC before, at day 10 and 2 years after resection of inflamed bowel segments. The data were correlated with neopterin, C-reactive protein and other standard parameters of disease activity. Preoperatively, mean sIL-2R concentration was 495 +/- 62 U/ml (mean +/- SEM; healthy controls; 210 +/- 25 U/ml; p less than 0.02) in CD and 705 +/- 120 U/ml (p less than 0.00002) in UC. The corresponding IL-6 serum concentrations were 37 +/- 6 U/ml in CD (controls: 11 +/- 0.6 U/ml; p less than 0.0036) and 33 +/- 6 U/ml (p less than 0.04) in UC. Two years postoperatively, sIL-2R was still elevated in 6 out of 9 patients in both disease groups. These patients did not differ from the remaining group with respect to disease activity. Serum IL-6, elevated in 7 patients with CD and in 6 patients with UC at day 10 postoperatively, had returned to normal in all patients by this time.(ABSTRACT TRUNCATED AT 250 WORDS)     

T lymphocyte activation in patients with active tuberculosis

Soluble interleukin-2 receptor (sIL-2R) is a marker of T lymphocyte activation. We measured the amount of serum sIL-2R in 35 patients with active tuberculosis before the initiation of antituberculous treatment. Twenty had pulmonary parenchymal lesion, 8 had tuberculous pleural effusion, and 7 had tuberculous lymphadenitis. The serum sIL-2R values were markedly elevated in patients with pulmonary tuberculosis (parenchymal lesion and pleural effusion) compared with patients with tuberculous lymphadenitis (2,612 +/- 536 versus 538 +/- 121 U/ml, p = 0.023), old, inactive tuberculosis (335 +/- 23 U/ml, p = 0.001), and normal control subjects (376 +/- 38 U/ml, p = 0.001). No significant difference was found between patients with parenchymal lesion and those with tuberculous pleural effusion. There was a positive correlation between serum sIL-2R values and the extent of disease on chest radiograph (r = 0.58, p less than 0.001). We conclude that the amount of sIL-2R may be a useful marker of disease activity and extent of involvement in patients with active tuberculous lesions.     

Elevated soluble interleukin-2 receptor and interleukin-2 receptor positive cells in carcinomatous pleural effusions

Soluble interleukin-2 receptor (IL-2R) level and IL-2R positive (IL-2R+) cells were studied in twenty patients with carcinomatous pleural effusions. The mean value of soluble IL-2R level in carcinomatous pleural effusions was 2930 +/- 1722 U/ml and that in sera was 965 +/- 610 U/ml. Soluble IL-2R level in carcinomatous pleural effusions was found to be significantly higher (p less than 0.001) than that in sera of patients with carcinomatous pleural effusions and that in transudates. Serum soluble IL-2R level in patients with carcinomatous pleural effusions was found, to be significantly higher (p less than 0.001) than that in normal controls (264 +/- 70 U/ml). We also studied IL-2R+ cells in pleural fluids and peripheral blood of patients with carcinomatous pleural effusions. The mean percentage of IL-2R+ cells in carcinomatous pleural fluid lymphocytes was 22.8 +/- 17.8%, as compared with 3.0 +/- 2.2% in peripheral blood lymphocytes of normal controls (p less than 0.001). No significant differences were observed among the cell types of lung cancer examined (adenocarcinoma, squamous, small cell and large cell carcinoma) and no correlation among levels of soluble IL-2R and IL-2R+ cell in either pleural fluid or blood. Our results suggest that in patients with carcinomatous pleural effusions, T cell-mediated active immune mechanisms (IL-2/IL-2R system) against cancer cells are more active in pleural fluid than in peripheral blood.     

Soluble interleukin 2 receptor in acute viral hepatitis and chronic liver disease

Serum levels of soluble interleukin 2 receptor were determined in patients with acute viral hepatitis and patients with various chronic liver diseases. In addition, the ability of peripheral blood mononuclear cells of patients with alcoholic cirrhosis to generate soluble interleukin 2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin 2 receptor concentrations in all patients with acute viral hepatitis were found to be significantly elevated (1,319 +/- 527 units per ml) during the first week after onset of disease, as compared to healthy control individuals (375 +/- 102 units per ml; p less than 0.0005) and declined toward normal levels during the course of the illness. Similarly, patients suffering from chronic liver disease such as alcoholic liver cirrhosis (1,172 +/- 507 units per ml), primary biliary cirrhosis (619 +/- 190 units per ml) or chronic active HBsAg+ hepatitis (941 +/- 357 units per ml) showed increased serum soluble interleukin 2 receptor concentrations (p less than 0.0005 vs. controls, respectively). In vitro mitogen stimulation of peripheral mononuclear cells derived from patients with alcoholic cirrhosis resulted in a soluble interleukin 2 receptor production not different from that seen in healthy individuals, suggesting that elevated soluble interleukin 2 receptor serum levels seen in this disease are not the result of an increased synthesis by circulating lymphocytes. Due to the ability of soluble interleukin 2 receptor to bind free interleukin 2--thus making it a potential immunoregulatory molecule--its high serum levels could explain some of the immunologic abnormalities observed in acute and chronic liver disease.     

Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity.

Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn's disease. sIL-2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn's disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn's disease is further evidence for in vivo immune activation occurring in this disease.     

Circulating soluble interleukin 2 receptor concentration is increased in both immunogenic and nonimmunogenic hyperthyroidism.

High serum concentration of soluble interleukin-2 receptor (sIL-2R) is considered a reliable marker of T lymphocyte activation. It has been recently reported that sIL-2R levels are increased in untreated Graves' disease. This finding has been interpreted as the consequence of an active autoimmune state, but the relevance of the thyroid function per se was not investigated. In the present study we assayed sIL-2R by ELISA in 20 normal subjects and in a series of patients with immunogenic (Graves' disease, GD) or nonimmunogenic (toxic adenoma, TA) hyperthyroidism. Significant increased concentrations of sIL-2R were found in 46 patients with untreated hyperthyroid GD (mean +/- SD: 1,683 +/- 1016 U/ml, vs 461 +/- 186 U/ml in normal controls, p less than 0.0001) and in 21 with untreated TA (1,111 +/- 617 U/ml, p less than 0.0001 vs normals). Restoration of the euthyroid state by antithyroid drugs or 131I administration was associated with a normalization of sIL-2R (516 +/- 174 U/ml in 38 patients with GD and 365 +/- 90 U/ml in 12 with TA; p = NS vs normals and p less than 0.001 vs the untreated state for both groups). A highly significant positive correlation between serum sIL-2R and free triiodothyronine (FT3) (r = 0.724, p less than 0.0001) or free thyroxine (FT4) (r = 0.698, p less than 0.0001) concentrations was found in combined sera obtained from all untreated and treated patients, irrespectively of the autoimmune or nonautoimmune nature of the underlying hyperthyroid disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma interleukin-2 and a soluble/shed interleukin-2 receptor in serum of patients with Crohn's disease. Effect of cyclosporin.

Circulating concentrations of interleukin-2 (IL-2) and a soluble or shed form of the IL-2 receptor (sIL-2R) were determined by enzyme-linked immunosorbent assays (ELISA) in 61 patients with chronic active Crohn's disease (CD) initially and during a three month placebo controlled trial of cyclosporin 5-7.5 mg/kg/day. The baseline median (25-75% range) plasma IL-2 concentration was 0.6 ng/ml (0.3-2.85 ng/ml) in patients who did not receive prednisolone, 0.5 ng/ml (0.23-3.4 ng/ml) in patients who did (not significant), and 0 ng/ml (0-0.07 ng/ml) in control subjects (p less than 0.00001). The corresponding median serum sIL-2R concentrations were 747 U/ml (580-1287 U/ml), 540 U/ml (422-616 U/ml) respectively in CD patients (p = 0.006) and 320 U/ml (268-406 U/ml) in control subjects (p less than 0.00001). Increased concentrations of plasma IL-2 and serum sIL-2R were seen in 66% and 81% of the patients, respectively. A fall in serum sIL-2R was only seen in patients who improved with cyclosporin treatment (p = 0.006). At month 3 the median serum sIL-2R concentration was 440 U/ml (400-668 U/ml) v 801 U/ml (534-1067 U/ml) in patients not responding to cyclosporin (p = 0.003). No changes occurred in the placebo group. These results suggest that the IL-2 dependent pathway of immune activation is upregulated in vivo in CD and that cyclosporin may interfere with this process.     

Whole gut lavage fluid interleukin-1β and interleukin-8 in smokers and non-smokers with Crohn''s disease in clinical remission

INTRODUCTION: Smoking in patients with Crohn's disease is associated with more frequent relapse. The mechanism responsible is unknown but a direct pro-inflammatory action on intestinal mucosa has been postulated. Mucosal inflammation in clinically inactive Crohn's disease predicts forthcoming relapse. Whole gut lavage fluid obtained after bowel cleansing with a polyethylene glycol electrolyte solution is an assessment of gut inflammation and immunity. AIM: To assess whether whole gut lavage fluid interleukin-1beta and interleukin-8 differed between smokers and non-smokers with clinically inactive Crohn's disease. METHODS: A total of 34 patients with inactive Crohn's disease (Crohn's disease activity index <150 and whole gut lavage fluid IgG concentration of <10 mg/ml) underwent whole gut lavage with interleukin-1beta and interleukin-8 analysed by enzyme-linked immunosorbent assay. Clinical details and blood markers of inflammation were collected. RESULTS: In this series, 14 patients smoked (10 females, mean age 44.3+/-14.3 years), 20 did not (12 females, mean age 40.7+/-14.3). Surgical resection was more common in smokers (12/14 vs 8/20, p<0.008). Whole gut lavage fluid IgG was significantly lower in smokers (median 1.5 mg/ml (range 1.0-8.0 mg/ml) vs median 3.5 mg/ml (range 1.0-7.0 mg/ml), p<0.05). Whole gut lavage fluid interleukin-1beta was also lower in smokers [median 14.5 pg/ml (range 2-72 pg/ml) vs 26 pg/ml (range 7-1700 pg/ml)], p<0.03. CONCLUSION: Markers of mucosal inflammation in inactive Crohn's disease are lower in smokers than non-smokers. This is against the hypothesis that nicotine exerts a direct pro-inflammatory action via interleukin-1beta and interleukin-8. Further research is required to elucidate the exact mechanisms involved.     

Serum lysozyme in Crohn's disease. A useful index of disease activity.

Serum lysozyme concentrations were determined in patients with clinically active and inactive Crohn's disease as well as in healthy volunteers. The mean serum lysozyme concentrations (+/- SE) for each group were as follows: controls, 8.8 +/- 0.4; active Crohn's disease, 20.8 +/- 0.8; and inactive Crohn's disease, 10.4 +/- 0.7 mug per ml. The mean lysozyme level was significantly greater in active Crohn's disease as compared to normal subjects (P less than 0.001) and patients with inactive disease (P less than 0.001). Moreover, in patients with clinically severe Crohn's disease there seems to be a trend toward greater lysozyme levels, as opposed to those with mild to moderately active disease. In patients followed serially during the course of their disease, serum lysozyme levels increased with exacerbations of the illness and decreased with clinical improvement. These findings suggest that the serum lysozyme concentrations may serve as a useful index of the activity of Crohn's disease and aid in monitoring the clinical course of such patients.     

Increased production of vascular endothelial growth factor by peripheral blood mononuclear cells in patients with inflammatory bowel disease

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic, vascular permeability-enhancing cytokine with overexpression in various pathological disorders, including tumour growth, chronic inflammation and tissue repair. Recent studies have shown significantly increased serum levels of VEGF in patients with inflammatory bowel disease. The origin of the circulating VEGF is still unknown. The present investigation examines the VEGF production by peripheral blood mononuclear cells (PBMCs) in patients with inflammatory bowel disease. METHODS: VEGF levels were measured in culture supernatants of unstimulated PBMCs of 27 patients with inflammatory bowel disease and 10 healthy volunteers using a solid phase ELISA. In addition, VEGF serum levels were determined. RESULTS: PBMCs of both active Crohn's disease patients (1142.6+/-483.9 pg/ml, P < 0.001, n = 12) and active ulcerative colitis patients (748.0+/-637.6 pg/ml, P = 0.006, n = 4) produced significantly higher amounts of VEGF compared with PBMCs of healthy volunteers (113.4+/-101.8 pg/ml, n = 10). In addition, there was a significantly increased VEGF production by PBMCs of patients with active disease compared with PBMCs of patients with quiescent Crohn's disease (261.6+/-254.8 pg/ml, P < 0.001, n = 7) and inactive ulcerative colitis (147.7+/-100.3 pg/ml, P = 0.02, n = 4). There was no significant difference in VEGF release between patients with inactive inflammatory bowel disease and healthy controls. CONCLUSIONS: Significantly increased VEGF production by PBMCs was found in patients with active Crohn's disease and active ulcerative colitis. The study helps to clarify one of the origins of the significantly enhanced VEGF serum levels in patients with active inflammatory bowel disease observed in recent studies.     

Postheparin plasma diamine oxidase in patients with small bowel Crohn's disease

Diamine oxidase (DAO) is an enzyme located almost exclusively in villus tip enterocytes of mammals. Its plasma activity, normally very low, is enhanced by intravenous heparin, which releases the enyzme from small bowel enterocytes into the blood. Plasma postheparin DAO (PHD) values have been shown to be significantly reduced in patients with malabsorption and villous atrophy and inversely correlated with 24-h fecal fat, thus suggesting that PHD reflects the mature enterocytic mass. We have assayed PHD in 51 patients with small bowel Crohn's disease by measuring the area under the plasma DAO curve over a 120-min period after an intravenous bolus of 15,000 IU of heparin. Postheparin plasma DAO was significantly lower (p less than 0.001) in patients (328 +/- 175 U/ml.min) than in 20 normal subjects (508 +/- 101 U/ml.min; range, 391-749). Postheparin diamine oxidase values were inversely correlated with Crohn's disease activity index (CDAI), but no correlation was found with extent of disease assessed radiologically by either double-contrast small bowel enema or barium meal follow-through. In 6 patients with active disease (CDAI, 297 +/- 99) and low PHD values (188 +/- 100 U/ml.min), the assay was repeated after a clinically effective course of antiinflammatory drugs. A significant increase in PHD values (388 +/- 112 U/ml.min) was observed (p less than 0.005). These data indicate that mucosal involvement is common in small bowel Crohn's disease and that PHD may be useful in assessing and monitoring mucosal damage in these patients.     

Elevated circulating platelet-derived microparticles in patients with active inflammatory bowel disease

OBJECTIVES: Platelet-derived microparticles (PDMPs) are active molecules involved in the hemostatic and inflammatory responses. To evaluate the changes in the platelet function in patients with inflammatory bowel disease (IBD), we measured circulating PDMP levels. METHODS: Twenty-five healthy controls, 44 patients with ulcerative colitis (UC), and 43 patients with Crohn's Disease (CD) were studied. The PDMP and soluble P-selectin (sP-selectin) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: In the healthy controls, the PDMP levels were 17.2 +/- 6.2 U/mL. Significant differences were not observed between the healthy controls and inactive UC patients (20.8 +/- 9.5 U/mL, n = 25) or between the healthy controls and inactive CD patients (17.6 +/- 7.8 U/mL, n = 24). In contrast, the PDMP levels were significantly higher in both active UC (49.2 +/- 33.6 U/mL, n = 19) and active CD (48.6 +/- 42.8 U/mL, n = 19) patients than in the healthy controls. A significant correlation was found between the PDMP levels and the clinical activity indexes (CAI) of UC patients (r = 0.65, p < 0.01, n = 44), and between the PDMP levels and Crohn's disease activity indexes (CDAI) (r = 0.72, p < 0.01, n = 43). Elevated PDMP levels in active patients were significantly reduced after remission. A significant correlation was observed between the PDMP levels and the sP-selectin levels (r = 0.60, p < 0.01, n = 122). CONCLUSION: Elevated circulating PDMPs in active IBD patients suggest a role for platelets in the pathogenesis of IBD.     

Accelerated production of nucleosome in cultured human mononuclear cells in untreated Graves' disease

The apoptosis of lymphocytes, which occurs in autoimmune diseases, is usually induced by the Fas/Fas ligand system. As the assay of nucleosomes produced by apoptotic cells can be used to quantitate apoptosis, we evaluated nucleosome and soluble Fas ligand (sFasL) levels of cultured mononuclear cells to clarify the apoptosis of mononuclear cells in patients with autoimmune thyroid diseases by enzyme-linked immunosorbent assay. Nucleosome levels of cultured mononuclear cells in patients with untreated Graves' disease were significantly higher (3.27+/-2.90 U/ml) than those of control subjects (1.39+/-0.24 U/ml) and euthyroid patients with treated Graves' disease (1.53+/-0.33 U/ml). Nucleosome levels of cultured mononuclear cells were positively correlated with sFasL levels (r=0.544, p<0.01). It is therefore likely that increased sFasL levels elicit apoptosis of these cells in untreated Graves' disease.     

Soluble interleukin-2 receptor in sera of patients with pulmonary tuberculosis

Interleukin-2 receptor, the complex of IL-2R-alpha and/or IL-2R-beta, is expressed mainly on T-lymphocytes, and the soluble form of IL-2R-alpha (sIL-2R-alpha) has been reported to be detected in the serum of patients with lymphoproliferative disorders or disease characterized by the cellular immune reaction. We measured serum sIL-2R-alpha levels among patients with pulmonary diseases and found that sIL-2R-alpha levels were significantly elevated in patients with active pulmonary tuberculosis (1,327 +/- 209 U/ml) and sarcoidosis (1,037 +/- 115 U/ml) when compared with healthy volunteers (468 +/- 49 U/ml, p less than 0.01). Among patients with pulmonary tuberculosis, the sIL-2R-alpha levels were high in sera from patients with extensive parenchymal lesions on the roentgenogram (2,745 +/- 705 U/ml) and patients with tuberculous pleurisy (2,111 +/- 679 U/ml). In contrast, the sIL-2R-alpha levels in tuberculous patients with minimal lesion (455 +/- 92 U/ml) or moderate lesion (1,082 +/- 189 U/ml) were not significantly elevated when compared with healthy volunteers. After the treatment with antituberculosis agents, serum sIL-2R-alpha levels decreased in accordance with improvement of roentgenographic findings and laboratory data. These results suggest that serum sIL-2R-alpha level may be useful as a monitor for the disease activity in patients with pulmonary tuberculosis.     

Tumor necrosis factor alpha production by peripheral blood mononuclear cells of patients with chronic liver disease

We investigated the production of tumor necrosis factor alpha by peripheral blood mononuclear cells of patients with chronic liver disease and its association with hepatitis activity. Tumor necrosis factor alpha production was measured with an enzyme-linked immunosorbent assay. Tumor necrosis factor alpha production by peripheral blood mononuclear cells stimulated with recombinant gamma-interferon of patients with chronic active hepatitis (5.8 +/- 4.0 units per ml, p less than 0.05) and patients with cirrhosis (4.1 +/- 2.1 units per ml, p less than 0.05) was significantly increased when compared with controls (2.5 +/- 1.6 units per ml). Tumor necrosis factor alpha production by peripheral blood mononuclear cells stimulated with a combination of recombinant gamma-interferon and recombinant interleukin 2 of patients with chronic persistent hepatitis (5.8 +/- 3.8 units per ml, p less than 0.05), patients with chronic active hepatitis (8.9 +/- 3.0 units per ml, p less than 0.001) and patients with cirrhosis (6.7 +/- 3.2 units per ml, p less than 0.05) was significantly increased in comparison with controls (3.3 +/- 1.8 units per ml). Tumor necrosis factor alpha production of patients with chronic active hepatitis was significantly higher than that of patients with chronic persistent hepatitis (p less than 0.05). There was a significant correlation (r = 0.5699, p less than 0.005) between tumor necrosis factor alpha production and histologic activity index in patients with chronic persistent hepatitis or chronic active hepatitis. These findings show that tumor necrosis factor alpha production is increased in chronic liver disease and that the increased tumor necrosis factor alpha production is related to hepatitis activity.     

Soluble interleukin-2 receptor in juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis (JRA) is a chronic, relapsing, inflammatory childhood disease characterized by arthritis and systemic inflammation. At present there is no rapid, efficient laboratory method of assessing disease activity and degree of immune activation. We measured serum soluble interleukin 2 receptor (sIL-2R) levels in 85 samples from 72 patients (22 samples from patients with systemic JRA, 34 from polyarticular patients, 29 from pauciarticular patients, of which 10 were HLA-B27 positive). The mean sIL-2R level from patients was 1565 U/ml, which is significantly elevated compared to control values of 594 U/ml (p less than or equal to 0.005). The highest levels were seen in patients with systemic JRA (mean value 2121 U/ml) while the lowest values were seen in HLA-B27 positive (+) patients (mean value 899 U/ml). Patients with clinically active disease had significantly elevated levels (mean value 1745 U/ml) compared to patients with inactive disease (mean value 846 U/ml, p less than or equal to 0.01). Highest levels were seen in patients with active systemic JRA (mean value 2419 U/ml) while patients with pauciarticular JRA and B27 + JRA had the lowest sIL-2R levels (1167 and 1045 U/ml, respectively). sIL-2R levels were elevated in all subgroups of clinically active patients compared to controls (p less than or equal to 0.0005). Three of the 4 patients with serial sIL-2R measurements showed falling values during the period of clinical remission. Using regression analysis and likelihood ratio tests, we found a significant correlation between sIL-2R levels and both disease activity and joint count (p less than or equal to 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Soluble interleukin 2 receptors in autoimmune chronic active hepatitis.

Children with uncontrolled autoimmune chronic active hepatitis have increased numbers of activated T lymphocytes expressing interleukin 2 receptors (IL2R). A soluble form of IL2R has recently been described whose proposed role is to downregulate T cell activation by competing for interleukin 2. We investigated whether a deficiency of soluble IL2R could account for the high concentrations of IL2R positive T lymphocytes in autoimmune chronic active hepatitis. Soluble IL2R was measured by enzyme-linked immunosorbent assay in the serum of 16 children with autoimmune chronic active hepatitis, eight with chronic liver disease due to hepatitis B virus infection, seven with Wilson's disease, nine with alpha 1 antitrypsin deficiency, and 15 healthy age matched controls. Soluble IL2R concentration was significantly higher in patients with autoimmune chronic active hepatitis than in healthy controls (mean (SEM) 475 (75) U/ml, 145 (8) U/ml respectively, p less than 0.01). Eleven patients who had active disease had significantly higher soluble IL2R concentrations (590 (89) U/ml) than the five cases with inactive disease (220 (36) U/ml, p less than 0.01). No difference was found between the controls and the patients with chronic liver disease due to hepatitis B infection, Wilson's disease, and alpha 1 antitrypsin deficiency. Percentages and absolute numbers of surface IL2R positive T cells as detected by immunofluorescence were significantly higher in the patients with autoimmune chronic active hepatitis (11.8% (1); 274/microliters (31)) than in controls (0.2% (0.1); 5/microliters (2), p less than 0.001), the highest values being found in those with uncontrolled disease. A significantly positive correlation was observed between concentrations of soluble IL2R and the percentage of T cells expressing IL2 receptors (r=0.67, p<0.001). These results indicate that the high levels of IL2R positive T lymphocytes characteristic of autoimmune chronic active hepatitis are not due to a deficiency of soluble IL2 receptors.