Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gut-associated lymphoid cells are modulated by several gut hormones. We postulated that lymphokine-associated-killer (LAK) cell cytotoxicity of lymphocytes isolated from the gut mucosa may be increased by substance P (SP). Intestinal lamina propria mononuclear cells (LPMC) and colonic cancer cells were isolated from operative specimens by successive mechanical and enzymatic dissociation methods. Effector LAK cells were induced by culturing LPMC with recombinant interleukin-2 at a concentration of 250 U/ml. Substance P (10(-5) M) was added to the culture medium. Targets consisted of fresh colon cancer cells, HT-29 (cultured human colon cancer cell line), and control cell lines. After 4 days of incubation, cytotoxicity was measured using a 4-h 51Cr release assay. LAK cells alone showed moderate cytotoxicity against HT-29 and none against fresh colon cancer cells. LAK cells generated in the presence of substance P showed moderate cytotoxicity against HT-29 and strong cytotoxicity against fresh colorectal cancer cells. The percentage of cytotoxicity +/- SEM at various effector to target ratios was [(*) denotes P < 0.05 compared with above]: [table: see text] We conclude that substance P significantly increases LAK cell cytotoxicity against fresh colon cancer cells, but not against cultured cells.
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PMID:Substance P increases in vitro lymphokine-activated-killer (LAK) cell cytotoxicity against fresh colorectal cancer cells. 127 74

Soluble interleukin-2 receptors (sIL2R) in plasma have been identified as a marker of lymphocyte activation. Lymphocyte activation as a manifestation of inflammation may be important in the pathogenesis of bronchopulmonary dysplasia (BPD). To test the hypothesis that infants with BPD have higher sIL2R levels, 12 infants with or at risk of developing BPD (GA +/- SD, 27 +/- 5 weeks; BW +/- SD 1,053 +/- 733 g) had plasma sIL2R levels determined and were compared to 20 infants being ventilated for respiratory distress syndrome (RDS) (GA +/- SD, 28 +/- 3.5 weeks; BW +/- SD, 1,133 +/- 390 g: P = NS for both GA and BW, t test). Tracheal aspirates in both groups were also analyzed for sIL2R levels. To control for the effects of postnatal age (PNA) and study weight (SW) on the sIL2R levels, another group of 16 nonventilated babies (NVB) had plasma analyzed for sIL2R (PNA +/- SD: 39 +/- 40 days NVB vs. 48 +/- 36 days BPD; P = NS); (SW +/- SD: 1391 +/- 250 g NVB vs. 1212 +/- 700 g BPD; P = NS). The following data were obtained for the plasma sIL2R levels (mean +/- SEM U/mL): RDS controls, 1,231 +/- 80; BPD infants, 1,790 +/- 120; NVB controls, 1,319 +/- 76; P = 0.0005 RDS vs. BPD and P = 0.002 BPD vs. NVB. There was no significant difference in the sIL2R levels for the infants at risk of developing BPD vs. the infants with established BPD. Also, when analyzed separately, infants at risk of BPD and the infants with established BPD had higher sIL2R levels than the RDS and NVB controls. No differences were noted in the tracheal sIL2R levels in the BPD vs. RDS groups. These data indicate that infants with BPD had significantly higher sIL2R levels in plasma than either RDS or NVB controls. Therefore, lymphocyte activation may play a role in the pathogenesis of BPD.
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PMID:Soluble interleukin-2 receptor levels in infants with bronchopulmonary dysplasia. 143 45

The use of adjuvant immunotherapy for the treatment of primary malignant brain tumors dates to studies performed in the 1960's and 1970's using non-specific immune stimulators. Although the theoretical designs have remained similar, recent advances in molecular biotechnology have produced a new group of recombinant cytokines, spawning a new generation of immunotherapy-based clinical trials. In contrast to other published Phase I/II studies, we have had highly encouraging preliminary results using lymphokine-activated killer (LAK) cells and recombinant human Interleukin-2 (rIL-2; Cetus, Emeryville, CA), when the patients' use of corticosteroids could be restricted while on study. Patients with recurrent grade 3/3 glioma received multiple cycles of autologous LAK cells and rIL-2, post-operatively, via an Ommaya reservoir implanted into the tumor cavity following re-operation. The overall median survival for 13 patients with grade 3/3 glioma has not yet been reached at 55 weeks following second surgery, [mean +/- SEM, 64.7 +/- 10.5 weeks], with 5 patients still alive. Three patients have had partial responses (PR) demonstrated by CT scanning. In addition, one patient with grade 2/3 glioma has had a complete response (CR), with the disappearance of all residual CT-documented enhancement and mass effect.
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PMID:The cellular immunotherapy of primary brain tumors. 144 66

Uremic patients suffer from various immunological alterations, whose pathogenesis is still unknown. Here, we studied 37 hemodialysis patients in order to investigate the role of prostaglandins (PGs) in uremic immunological deficiency, specifically in relation to interleukin-2 (IL-2) synthesis. We confirmed previous published data on deficient response to PHA in chronic renal failure patients (cpm, mean +/- SEM: 15,400 +/- 2,100 in uremics vs. 29,500 +/- 3,380 in controls, p < 0.04) and established a correlation between this deficiency and diminished IL-2 synthesis (r = 0.619, p < 0.05). The direct measurement of PGs in lymphocyte cultures showed greatly increased concentrations in the presence of uremic serum (US). We found that PGs synthesis can be inhibited by up to 80% if cultures are supplemented with indomethacin (IND--a cyclooxigenase inhibitor) or by removal of monocytes (producers of PGs). Both methods situated the uremic proliferative response within the normal range in cultures with FCS, and close to the normal range in cultures with US. We observed a deficit of IL-2 in hemodialysis patients (means +/- SD: 8,940 +/- 6,420 in uremics vs. 16,900 +/- 3,890 in controls). Addition of exogenous IL-2 normalized lymphocyte response even in US cultures, with no additive effect between PGs inhibition and exogenous IL-2 except in US cultures. It is suggested that IL-2 deficit of uremics depends, at least in part, on an increase in PGs synthesis induced by US.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-2 deficit in hemodialysis patients. Role of prostaglandins. 146 8

Interleukin-2 (IL-2) and T cell subpopulations were evaluated in children with rheumatic heart disease (RHD). Three groups were included: 13 patients with active RHD, 12 with non-active RHD, and 14 control children. Serum IL-2 and T cell subpopulations were measured by radioimmunoassay and monoclonal antibodies respectively. Patients with active RHD showed a significant increase in IL-2 concentrations and helper:suppressor (H:S) ratio compared with controls with a mean (SEM) IL-2 of 3.48 (0.62) v 1.26 (0.16) U/ml and H:S ratio 2.31 (0.14) v 1.66 (0.04). There was a significant decrease in T suppressor (CD8+) and pan T (CD3+) cells compared with controls with a mean (SEM) for CD8+ of 23.75 (1.19) v 32.23 (0.56)% and CD3+ of 79.55 (0.94) v 85.00 (0.11)%. Patients with non-active RHD showed a significant decrease only in the CD3+ cells (78.20 (0.20)%) when compared with controls. A deficiency of CD3+ cells is a constant finding in patients with RHD, whether the disease is active or not. There was a significant increase in IL-2 concentration with a significant decrease in CD8+ cells in patients with active RHD in comparison with the non-active group (mean (SEM) IL-2 of 3.48 (0.62) v 1.85 (0.24) U/ml and CD8+ of 23.75 (1.19) v 28.83 (1.91)%). Thus an increase in IL-2 and a decrease in CD8+ cells may be related to rheumatic activity. T helper (CD4+) cells did not differ significantly between groups.
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PMID:Interleukin-2 in relation to T cell subpopulations in rheumatic heart disease. 147 90

The presence of immunoreactive interleukin-1 (IL-1) and interleukin-2 (IL-2) in human follicular fluid obtained at the time of oocyte collection for in-vitro fertilization was ascertained by radioimmunoassay. In group I (20 fluids from 20 patients), the concentrations of IL-1 were 0.9 +/- 0.06 and 1.9 +/- 0.04 (mean +/- SEM) fmol/l in follicular fluid and plasma respectively. A positive correlation existed between IL-1 levels in follicular fluid and plasma (r = 0.56, P less than 0.01). Concentrations of IL-2 were 3.5 +/- 0.2 and 6.1 +/- 0.3 fmol/l in follicular fluid and plasma respectively. A positive correlation of IL-2 levels was also found between follicular fluid and plasma (r = 0.65, P less than 0.01). There was no association between IL-1, IL-2 and steroid levels, regardless of whether they were compared in follicular fluid or plasma. Group II was composed of a series of fluids (two to seven samples for each of seven patients) in which the follicular concentrations of IL-1 and IL-2 did not show a positive correlation with the volume of follicular fluid or the concentrations of follicular fluid steroids. It is concluded that human preovulatory follicular fluid contains immunoreactive IL-1 and IL-2. The role of IL-1 and IL-2 in ovarian physiology remains to be determined.
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PMID:Concentrations of immunoreactive interleukin-1 and interleukin-2 in human preovulatory follicular fluid. 157 24

Deficient cellular cytotoxic mechanisms are present in neonates, contributing to their increased susceptibility to certain viruses, notably herpes simplex virus (HSV). Significant lymphokine-activated killer (LAK) cell activity has been described in cord blood, suggesting a possible role for LAK and/or interleukin-2 (IL-2) therapy in newborns with serious viral infections. The effect of HSV (type 1) on the activation of cord versus adult LAK cells was investigated by adding virus (multiplicity of infection, MOI = 10) to cells that had been previously incubated for 4-6 days with IL-2 (50-100 U/ml). The cells were then tested 24 h after virus exposure for cytotoxic activity against 51Cr-labelled K562 and Raji target cells. HSV inhibited LAK cytotoxicity of adult cells against K562 by 44% (72 +/- 2.4%, SEM; specific lysis to 40 +/- 6.2%, n = 15) and by 62% against Raji targets (50 +/- 5.6 to 19 +/- 4.4%). A similar degree of inhibition was observed for cord cells against K562 (76 +/- 2.0 to 46 +/- 5.3%) and Raji (60 +/- 4.6 to 24 +/- 6.2%). The degree of inhibition was correlated with the dose of virus in dose-response experiments. Inhibition was also noted with irradiated (10,000 rad) but not with heat-inactivated (56 degrees C for 60 min) virus. No inhibition was found when virus was added directly to the cytotoxic assay or when virus was added at the initiation or end of culture of cells with IL-2 (i.e. day 0 or day 5-7). In contrast, HSV stimulated cytotoxic activity against both the natural killer (NK)-sensitive (K562) and NK-resistant (Raji) targets in cells not incubated with IL-2. The cytotoxicity of adult cells incubated with infectious HSV (MOI = 10) for 5-7 days increased from 5.5 +/- 1.9% in the absence of virus to 25 +/- 6.0% against K562 in the presence of virus and from 3.5 +/- 1.0 (no virus) to 16 +/- 4.3% (with virus) against Raji targets (n = 8). The cytotoxicity of cord cells was also stimulated, but to a lesser degree. Irradiated virus also stimulated cytotoxic activity but to a lesser degree in cord cells. Virus-induced nonspecific cytotoxicity may represent an important component of the host's antiviral defense that is present at birth, but somewhat diminished compared to normal adults.
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PMID:Effects of herpes simplex virus on induced cell-mediated cytotoxicity in neonates and adults. 166 47

The toxicity due to interleukin-2 (IL-2) strongly resembles the clinical picture seen during septic shock. In septic shock activation of polymorphonuclear neutrophils (PMN) and the complement system contribute significantly to the pathophysiology of the condition. We therefore investigated whether similar events contributed to the toxicity observed with IL-2. Four patients received seven cycles of escalating dose IL-2 (18.0 to 72.0 X 10(6) IU m-2 day-1) and 16 were treated with 20 cycles of fixed dose IL-2 (12.0 or 18.0 X 10(6) IU m-2 day-1). Toxicity, as judged by hypotension (P = less than 0.005) and capillary leakage (fall in serum albumin 18.2 vs 4.0 gm l-1; P = less than 0.0005 and weight gain 4.0 vs 1.2 kg; P = less than 0.025) were worse with the esc. dose protocol. PMN became activated following IL-2 with mean peak elastase/alpha 1-antitrypsin (E alpha 1 A) and lactoferrin values of 212 (SEM = 37) and 534 (SEM = 92) ng ml-1 respectively occurring 6 h after the IL-2. Peak values for the esc. dose IL-2 group being generally higher than 500 ng ml-1. Activation of the complement cascade was evidenced by a dose dependent elevation of peak C3a values (fixed dose 9.1 (SEM = 0.6); esc. dose 25.7 (SEM = 6.33); P = less than 0.005) on day 5 of IL-2. There was a significant correlation between C3a levels and the degree of hypotention during the first 24 h after IL-2 (r = 0.91) and parameters of capillary leakage such as weight gain and fall in serum albumin (r = 0.71). These data suggest that activation of PMN initiates endothelial cell damage which subsequently leads to activation of the complement cascade. This latter system then contributes to the haemodynamic changes and capillary leakage seen in IL-2 treated patients.
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PMID:The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant interleukin-2. 173 48

Tumor-infiltrating lymphocytes (TIL) were isolated from 22 human primary and metastatic liver tumors, and expanded in vitro in the presence of either interleukin-2 (IL-2, 100 U/ml) plus tumor necrosis factor alpha (TNF alpha, 1000 U/ml), IL-2 (1000 U/ml) plus IL-4 (1000 U/ml) or IL-2 (1000 U/ml) alone. TIL proliferated in culture in 20/22 cases. Among different cytoline combination, TNF alpha and IL-2 were most effective in promoting the outgrowth of CD3+CD8+T lymphocytes (mean +/- SEM: 90% +/- 5) in the cultures of TIL from primary liver tumors. Cytotoxicity against autologous tumor cells was demonstrated in all early cultures of TIL from primary liver cancers in the presence of IL-2 plus TNF alpha. In contrast, cultures of TIL derived from colon cancer metastatic to liver had significantly lower levels of autotumor cytotoxicity and proportions of CD3+CD8+ cells (40% +/- 13) than those of TIL from primary liver tumors. The addition on day 0 of interferons (alpha or gamma) to TIL cultured in the presence of TNF alpha and IL-2, significantly augmented cytotoxicity against autologous tumor. In contrast, incubation of TIL in the presence of IL-4 and IL-2 did not result in increased autotumor responses in the cultures of TIL from primary liver tumors. The expansion (-fold) of TIL (day 30) cultured in the presence of IL-2 alone compared to that in the presence of TNF alpha and IL-2 was significantly greater for hepatocellular carcinoma (median, 280 vs 260) than for autologous peripheral blood lymphocytes (36 vs 27), cholangiocarcinoma (42 vs 51) or TIL from metastatic colon cancer (39 vs 30). Outgrowth of TIL in IL-2 plus TNF alpha offers an opportunity for in vitro enrichment in cells with autotumor cytotoxicity in primary liver tumors. However, this cytokine combination was unable to promote and sustain growth of autotumor effectors from TIL in metastatic liver cancer.
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PMID:Effects of cytokines on in vitro growth of tumor-infiltrating lymphocytes obtained from human primary and metastatic liver tumors. 184 44

Pleural fluid and serum soluble Interleukin-2 receptors (sIL-2R) were measured by an enzyme-immunoassay in 13 patients with tuberculous pleurisy, in 28 patients with carcinomatous pleurisy and in 17 transudates from patients with congestive heart failure. Significantly higher values of sIL-2R were observed in exudative than in transudative (mean +/- SEM = 713 +/- 111 U/ml) pleural fluid samples, the highest being found in tuberculous (3777 +/- 501 U/ml) and the intermediate in carcinomatous exudates (1981 +/- 160 U/ml) (p less than 0.0001; on way ANOVA). Serum sIL-2R were significantly higher in carcinomatous and transudative groups than in age- and sex- matched controls (p less than 0.002; one way ANOVA), while there was no significant difference between the tuberculous group and controls. The pleural/serum sIL-2R ratio was significantly higher in tuberculous (5.32 +/- 0.60), than in carcinomatous pleurisy (2.67 +/- 0.20) and higher still than in transudates (0.76 +/- 0.10) (p less than 0.001; one way ANOVA). In conclusion, the pleura/serum sIL-2R ratio may be a helpful parameter in differentiating tuberculous from carcinomatous pleurisy and an additional confirmatory one for distinguishing transudates from exudates.
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PMID:Pleural fluid and serum soluble interleukin-2 receptors in pleural effusions. 188 73


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