Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin E2 (PGE2)-mediated monocyte (M phi) suppressor activity and inadequate T-helper cell function represent the mechanistic keystones of trauma-induced impairment of cell-mediated immunity (CMI). In a prospective randomized trial, the immunorestorative potential of a combined therapy with the thymomimetic substance Thymopentin (TP-5; Timunox, Cilag GMBH, Sulzbach, FRG) and the cyclooxygenase inhibitor indomethacin (Indo) in 60 patients (mean age, 63 +/- 2 years) undergoing open heart surgery was studied. Perioperative immunologic screening was carried out on days -2, 3, 1, 5, and 7 and included the in vivo delayed type hypersensitivity (DTH) skin response, phenotyping for peripheral blood mononuclear cell (PBMC)-specific and nonspecific induction of lymphoproliferative responses, in vitro interleukin-2 (IL-2) synthesis, as well as the serum concentration of D-erythro-Neopterin (NPT) and of gamma interferon (gamma-IFN). The study protocol comprised three groups (n = 20): PA (Indo 150 mg administered intravenously on days 0 to 5), PB (TP-5 administered subcutaneously on days 0, 2, 4, and Indo), and PC (control). In contrast to PC, significant immunorestoration could be demonstrated in PB, as DTH scores on day 7, as well as proliferative responses in cell cultures were not depressed after operation (p less than 0.05). Cell-surface receptor expression for the CD3+, CD4+, and IL-2 receptor-positive (IL-2R+) lymphocyte subpopulations following surgery was reduced to 75% of baseline values in PC, while in PB, receptor protection for CD4+ and IL-2R+ subpopulations (more than 15% above baseline) was observed. Interleukin-2 synthesis (average baseline value, 0.7 + 0.08 U/mL) in cell cultures of PC was massively suppressed, with lymphokine concentrations in the supernatants never more than 0.27 +/- 0.05 U/mL. In PA cultures, IL-2 synthesis was impaired as well but not as precipitously as in PC. In contrast, in PB cultures, the average IL-2 production on consecutive postoperative days was never below baseline values. This study clearly demonstrates that the combined Indo/TP-5 therapy is superior to single Indo administration and can adequately preserve and/or restore intact M phi T-cell interaction and thus appears to be a feasible approach to maintain normal host defense activity in traumatized individuals.
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PMID:Immunomodulatory therapy with thymopentin and indomethacin. Successful restoration of interleukin-2 synthesis in patients undergoing major surgery. 192 8

The effect of thymopentin treatment was investigated in immunocompromised elderly subjects. Thymopentin was able to increase IL-2 production and IL-2 receptor expression, as assessed on PHA-activated blasts by percentage of Tac-positive cells and response to exogenous IL-2. After treatment, an increased precursor frequency, estimated by limiting dilution analysis, of PHA-responding lymphocytes was observed in two out of six subjects tested. In vitro experiments with thymopentin show that the drug was able to enhance blastogenesis by PHA of elderly lymphocytes but not of adult cells. These results indicate that (a) the increased IL-2 synthesis/IL-2 receptor expression may be the crucial mechanism of the immunopotentiating activity of the drug in elderly subjects and (b) an increased intrinsic T-cell responsiveness seems to be responsible for this immunopotentiating activity, although an increase in the size of the responsive T-cell pool could not be excluded.
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PMID:In vivo immunopotentiating activity of thymopentin in aging humans: modulation of IL-2 receptor expression. 313 50

A detailed analysis of the immune system response has been performed during the development and progression of dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. For this aim, a number of immune parameters (thymocyte and splenocyte proliferative response to T-dependent mitogens, antibody production, lymphocyte subset phenotyping, interleukin 2 receptor expression in resting and activated lymphocytes, thymus morphology and morphometry), were correlated with tumor appearance and growth at different (-7, 0, +15, +30, +60, +90, and +120 days) time intervals after intragastric administration of DMBA, in the absence or the presence of a concomitant treatment with the thymic pentapeptide thymopentin (TP5). A profound and time-dependent immunosuppression characterized the treatment with the carcinogen. Both cell-mediated and humoral immune responses showed a 50% inhibition 2 weeks after DMBA administration, with a peak after 30 days, followed by a plateau until 120 days of observation. The mechanism responsible for reduced ability of thymocytes and splenocytes to respond to both Con-A and PHA was explained by the significant inhibition of one of the key steps of T cell activation, namely the expression of IL-2 receptor in lymphocytes from DMBA-treated animals. The flow cytometric analysis of lymphocyte subpopulations revealed an important reduction in the overall populations of thymocytes and splenocytes. At the thymus gland level, a dramatic reduction of double positive CD4+CD8+ and a decrease of CD4+CD8- and CD4-CD8+ were observed, together with a marked atrophy of the thymic cortex, and impairment of the thymic microenvironment. One hundred and twenty days after DMBA administration, approximately 60 to 70% of the animals developed tumors with a mean tumor surface area of 2.88 +/- 0.86 cm2, and a number of 2.44 +/- 1.0. Treatment with TP5 (100 ng/animal, three times a week, starting a week before DMBA), produced specific effects on different immune compartments and tumoral growth, characterized by a significant reversal of immune depression with a stimulatory effect measured on lymphoproliferative assays, lymphocyte subset distribution, and IL-2 receptor expression. Moreover, thymic atrophy was almost completely prevented in TP5 treated animals. Of major interest, a significant delay in the appearance and growth of tumors was observed in TP5 treated rats. When DMBA-treated animals were followed for the entire observation period (0-120 days) and the immune responsiveness correlated according to tumor progression, stability, or regression, a positive correlation was calculated between the degree of immune system depression and the individual rate of tumor growth; in TP5-treated rats the majority of the tumors were static or regressing tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The immune system response during development and progression of carcinogen-induced rat mammary tumors: prevention of tumor growth and restoration of immune system responsiveness by thymopentin. 831 80