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

The production and targeting of a major T cell derived lymphokine, Interleukin 2 (IL-2), were studied in 23 uremic patients undergoing regular hemodialysis treatment and 20 uremic patients prior to the onset of renal replacement therapy. In hemodialyzed patients, abnormally increased proportions of circulating T cells spontaneously expressing high affinity IL-2 receptors (IL-2 Rec) were detected: they bound a monoclonal antibody specifically directed to the IL-2 Rec 55 kDa chain (Tac antigen) (mean +/- SEM: 7.12 +/- 0.81% in patients vs. 2.15 +/- 0.39% in normal controls, P less than 0.0001) and significantly proliferated in presence of human recombinant IL-2 alone (mean +/- SEM: 5438 +/- 729 cpm in patients vs. 1647 +/- 244 cpm in normal controls). Hemodialyzed patients also exhibited significantly increased serum levels of soluble IL-2 receptor (mean +/- SEM: 4036 +/- 947 U/ml in patients vs. 253 +/- 29 U/ml in normal controls. P less than 0.001). Moreover, a significantly decreased IL-2 activity was detected in the supernatants of stimulated T cells from hemodialyzed patients (mean +/- SEM: 0.93 +/- 0.12 U/ml in patients vs. 2.49 +/- 0.22 U/ml in normal controls, P less than 0.0001). In nine hemodialyzed patients who were analyzed before and immediately after the hemodialysis session no acute modifications of the various parameters analyzed were detected. Although less profound, a similar pattern of T cell abnormalities was observed in the uremic non-hemodialyzed patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:In vivo T cell preactivation in chronic uremic hemodialyzed and non-hemodialyzed patients. 268 33

Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from 12 uremic patients undergoing intermittent hemodialysis were tested for their capacity to produce IL-2 and BCGFs and to respond to these soluble mediators. IL-2 and BCGF activities were determined by means of two biological assays (proliferation of IL-2-dependent cytotoxic T-cell line CTLL-2 and of anti-human IgM (mu chain)-stimulated normal B cells, respectively) in the supernatants of phytohemagglutinin A-stimulated T-cell cultures. IL-2 activity was significantly decreased in patients as compared to normal controls (mean +/- SEM, 0.28 +/- 0.09 unit per ml) in hemodialyzed patients versus 1.02 +/- 0.16 units per ml in normal controls). This profound abnormality contrasted with the normal activity of the BCGFs that was invariably observed in the same supernatants. A similar dissociation was detected when analyzing the sensitivity of uremic B and T cells to exogenous purified lymphokines. Anti-IgM (mu chain)-stimulated uremic B cells exhibited a normal response to recombinant IL-2 and to chromatography-purified BCGF I and BCGF II. Resting B cells did not show any increased reactivity to these lymphokines. In contrast, whereas in normal controls recombinant IL-2 exclusively induced the proliferation of T cells that had been previously activated by a mitogen, resting T cells from uremic patients were highly responsive to exogenous IL-2. This abnormal response was paralleled by significantly increased proportions of peripheral T cells recognized by the anti-Tac monoclonal antibody that specifically binds to the IL-2 receptor. These data clearly show the existence in hemodialyzed patients of abnormally high proportions of T cells presenting phenotypic and functional signs of preactivation. This increased T-cell IL-2 receptor expression may offer an explanation to the deficient IL-2 activity observed in patients' supernatants (by inducing increased absorption of the lymphokine). The potential relevance of these preactivated T cells to the depressed cell-mediated immunity observed in hemodialyzed patients is outlined.
 ...
PMID:Presence of preactivated T cells in hemodialyzed patients: their possible role in altered immunity. 309 9

Sepsis remains the major cause of postresuscitation death after hemorrhage and trauma. The high incidence of infection in this setting has been attributed to host defense abnormalities, including dysfunction in cell-mediated immunity. To elucidate the interaction between injury and host defense mechanisms, we measured interleukin 2 (IL 2) production by peripheral blood mononuclear cells in 21 patients immediately after unanesthetized, accidental hemorrhage or trauma. Interleukin 2 production in minimally injured patients (0.63 +/- 0.14 [SEM] units) was similar to that found in control, uninjured subjects (0.68 +/- 0.17 units). Compared with control patients, IL 2 production was reduced 56% in patients with moderate injury and 85% in patients with severe injury. There was significant correlation between the severity of injury and the reduction in IL 2 production. Lymphocyte proliferative response to phytohemagglutinin was reduced in patients with moderate and severe injury, and the reduction in proliferative response was significantly correlated with injury severity. These results indicate that marked abnormalities in cell-mediated immune function, as determined by IL 2 production, occur immediately after hemorrhage and accidental injury.
 ...
PMID:The effects of hemorrhage and trauma on interleukin 2 production. 387 97

Interleukin 2 (IL2) was injected peritumorally and intranodally in 36 patients with unresectable squamous cell carcinoma of the head and neck enrolled in an Eastern Cooperative Oncology Group-sponsored phase Ib trial (EST P-Z388). Groups of 6 patients received escalating doses(200, 2 x 10(3), 2 x 10(4), 2 x 10(5), 2 x 10(6), and 4 x 10(6) units) of IL2 daily 5 times/week for 2 weeks. Tumor biopsies were obtained before and after IL2 therapy. Tumor tissue was provided for histology, and the remaining fresh tissue was divided for snap-freezing in -75 degrees C and for separation of tumor-infiltrating lymphocytes (TIL) and tumor cells. Immunophenotyping of TIL performed on cryostat sections of paired pre- and post-IL2 biopsy tissues showed increases after IL2 therapy in the number of T-cells (P = 0.005), natural killer (NK; CD16+) cells (P = 0.0001), CD25+ cells (P = 0.004), and HLA-DR+ cells (P = 0.001) accumulating in the tumor stroma. In the tumor parenchyma, NK cells (P = 0.0001) and HLA-DR+ cells (P = 0.003) were increased after IL2 therapy. The T:NK cell ratios in the tumor stroma and parenchyma were decreased after therapy, suggesting selective accumulation of NK cells. By flow cytometry, TIL recovered from post-IL2 biopsy tissues were enriched (P < 0.05) in CD3-CD56+ (NK) cells. In situ hybridization with [35S] cDNA probes for cytokines and IL2 receptors indicated that the numbers of cells expressing mRNA for IL2, tumor necrosis factor alpha, IL1-beta, gamma-interferon, transforming growth factor beta, and IL2 receptor p55 or p70 were increased in post-IL2 biopsy tissues as compared to pre-IL2 tissues. Cytolytic activity of TIL isolated from post-IL2 tissues was also increased, as determined in 4-h 51Cr release assays against K562 targets (12 +/- 3 mean lytic units/10(7) cells +/- SEM pre-IL2 versus 46 +/- 13 post-IL2; n = 16) and against autologous tumor (13 +/- 8 versus 68 +/- 26; n = 9). Fresh TIL of one clinical responder showed relatively high levels (195 lytic units) of autotumor cytotoxicity after IL2 therapy versus no activity prior to therapy. In the blood, NK and lymphokine-activated killer cell activity, and percentages of CD3-CD56+ NK cells and of activated (CD25+) T-lymphocytes were increased for all doses of IL2.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Evidence for local and systemic activation of immune cells by peritumoral injections of interleukin 2 in patients with advanced squamous cell carcinoma of the head and neck. 824 20

Interleukin 2 (IL2) has well recognized pleiotropic effects on the activation, differentiation and proliferation of lymphoreticular cells, mediated via its specific membrane-bound receptors, but its effect on human solid tumour cells is poorly characterised. This study has used the A549 tumour cell line, derived from a human lung carcinoma, to demonstrate the presence of the interleukin 2 receptors (p70/75 beta and/or p55 alpha components) and to document functional activity. Immunohistochemical techniques demonstrated large amounts of the p70/75 beta chain of the interleukin 2 receptor, which is necessary for IL2 internalization, receptor signal transduction and mediation of the biological effects of IL2. In contrast, the p55 alpha chain was detected minimally and sparsely. In addition we documented the presence of IL2 in the nucleus of the A549 cells. The addition of exogenous rIL2 (10-500 IU/ml), to the culture medium of A549 cells over 48 hours resulted in a significant stimulation of DNA synthesis, as assessed by tritiated thymidine uptake. The results were; 9335+/-365, 12669+/-271, 12889+/-255, 19448+/-1427, 20189+/-1004 and 22586+/-1334 CPM, at 0 IU/ml, 10 IU/ml, 50 IU/ml, 100 IU/ml, 250 IU/ml and 500 IU/ml, respectively (means+/-SEM), and were significantly increased when compared with control cultures, p<0.001). These results may have important implications in our understanding of tumour-host interactions and in future strategies involving immunotherapy.
 ...
PMID:Expression of the intermediate affinity interleukin-2 receptor by a human solid tumor-cell line - evidence for functional-activity. 2155 63