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)

Both immunostimulatory and immunosuppressive events would occur during the immunotherapies of cancer, including interleukin 2 (IL-2) therapy. The marked increase in soluble IL-2 receptor (SIL-2R) levels during IL-2 therapy could represent a potentially negative biological effect, because of the receptor's capacity to bind IL-2 and compete for it with IL-2 cell surface receptor. Since it has been observed that macrophages stimulate in vitro the release of SIL-2R, a study was started to evaluate in vivo the role of macrophages in IL-2-induced SIL-2R rise by measuring neopterin, which is a marker of macrophage activity. The study included 9 advanced renal cancer patients, treated subcutaneously with IL-2 at 1.8 x 10(6) IU/m2 twice daily for 5 days/week for 6 weeks. Both SIL-2R and neopterin serum mean levels significantly increased during IL-2 treatment, and the highest concentrations were reached on the second week of therapy. SIL-2R rise was significantly correlated to that of neopterin. This study, by showing a positive correlation between SIL-2R and neopterin rise, would suggest a macrophage involvement in the stimulation of SIL-2R release during IL-2 immunotherapy of cancer.
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PMID:Increase in soluble interleukin-2 receptor and neopterin serum levels during immunotherapy of cancer with interleukin-2. 183 85

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

Gamma interferon (gamma-IFN), lipopolysaccharide (LPS)-gamma or interleukin-2 (IL-2)-induced tumor necrosis factor alpha (TNF alpha) production by both macrophages and peripheral blood mononuclear cells (PBMC), was increased in the presence of neopterin. Addition of neopterin caused an increased level of TNF alpha, but did not affect the kinetics of the TNF alpha production, which showed peak levels of cytotoxic activity 4 h after stimulatory treatment. Using anticytokine antibodies, we concluded that the neopterin effect was mainly gamma-IFN mediated, and only slightly affected by anti IL-2 receptor antibodies. The neopterin augmented TNF alpha production can be attributed to an immunological role for neopterin in the enhancement of cell-mediated immune (CMI) response.
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PMID:Neopterin augmentation of tumor necrosis factor production. 195 36

Relationships among four serologic activation markers and T cell subsets were measured in HIV-seropositive former blood donors (N = 64) and seronegative controls (N = 61). Significant correlations were observed for the HIV group in pairwise comparisons of soluble IL-2 receptor (sIL-2R), beta 2-microglobulin (beta 2M), neopterin (NEOP), and soluble CD8 (sCD8). CD4 cell levels (number/microliter) in the HIV group showed significant negative correlation with all four serologic markers; CD8 cell levels, in contrast, showed no significant correlation with any serologic activation marker measured. Significant correlations were observed, however, among various cell surface activation markers and serologic activation markers. Specifically, the proportion of CD8 cells expressing CD45RA showed significant negative correlations with NEOP and B2M levels, whereas the proportion of CD8 cells expressing HLA-DR showed significant positive correlations with B2M and sIL-2R levels. Further, the proportion of CD8 cells expressing CD38 showed significant positive correlations with all four serologic activation markers. These findings indicate that sIL-2R, B2M, NEOP, and sCD8 show similar quantitative changes and correlational relationships to CD4 cell destruction in HIV infection; they differ, however, in their relationships to proportional changes in activated CD8 cell subsets.
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PMID:Interrelationships between serologic markers of immune activation and T lymphocyte subsets in HIV infection. 196 60

Most of the cells found in lung parenchyma in patients with idiopathic pulmonary fibrosis are activated T lymphocytes and macrophages. The serum levels of three markers of cell mediated immunity were measured in 20 patients with idiopathic pulmonary fibrosis, in 20 normal subjects and in 12 patients with sarcoidosis to evaluate their clinical and prognostic significance in idiopathic pulmonary fibrosis. The three markers were: soluble CD8 (from activated suppressor-cytotoxic lymphocytes), soluble interleukin (IL)-2 receptors (from activated T cells and macrophages), and neopterin (from activated macrophages). Patients with idiopathic pulmonary fibrosis had higher levels of all three markers than the control subjects. Soluble IL-2 receptor and neopterin tended to be lower (though not significantly) in patients with idiopathic pulmonary fibrosis than in those with sarcoidosis, whereas soluble CD8 was similar in the two groups of patients. No correlation was found between soluble IL-2 receptors or soluble CD8 and the clinical, radiological, and physiological measures of disease activity or with clinical outcome (after a mean follow up of 23 months). Tumour necrosis factor levels were also determined. Only 30% of patients with idiopathic pulmonary fibrosis or sarcoidosis had detectable circulating tumour necrosis factor; these patients had a lower percentage of bronchoalveolar lavage fluid neutrophils in their lavage fluid. Tumour necrosis factor levels did not correlate with clinical measures of severity or outcome. Thus our data support the hypothesis that cell mediated alveolitis occurs in idiopathic pulmonary fibrosis. They do not, however, provide evidence to support the use of these markers of cell mediated immunity to monitor the clinical course in these patients.
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PMID:Idiopathic pulmonary fibrosis: can cell mediated immunity markers predict clinical outcome? 211 91

Neopterin concentrations in body fluids of HIV-1 seropositives provide predictive information. In 1986, we examined serum and urine neopterin concentrations in 29 HIV-1 seropositives. Serum levels of soluble IL-2 receptor (sIL2R), soluble CD8 (sCD8), tumour necrosis factor alpha (TNF-alpha) and circulating immune complexes (CIC) were retrospectively analysed in 1989. All individuals had increased serum and urine neopterin, sIL2R and CIC concentrations, 27/29 had increased sCD8 concentrations, whereas all had normal TNF-alpha levels. During a 3-year follow-up, high urine and serum neopterin concentrations were significantly associated with progression to AIDS and with the occurrence of AIDS-associated death. Both neopterin variables were of similar predictive value (p less than 0.001, generalized Wilcoxon test). sIL2R concentrations were of borderline significance in predicting the onset of AIDS (p = 0.05). All other parameters lacked predictive information in our study. We conclude, that chronic immune activation is detectable in almost all HIV-1 seropositives. Chronic immune activation may be associated with HIV-1 replication and may contribute to the immunopathology of HIV-1 infection.
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PMID:Immune activation markers to predict AIDS and survival in HIV-1 seropositives. 212 76

Stimulation of peripheral blood mononuclear cells (PBMC) by the mitogenic lectins, phytohaemagglutinin (PHA) and concanavalin A (conA), the lymphokine gamma-interferon (gamma-IFN) and interleukin-2 (IL-2) and the pterin neopterin, caused an increased release of neopterin from those cells, with peak levels after 7 days of stimulation. In contrast to gamma-IFN, IL-2 and neopterin failed to induce neopterin release from purified macrophages. IL-2- and neopterin-induced release of neopterin from PBMC is not dependent on proliferation and is partially inhibited by the addition of anti gamma-IFN or anti IL-2 receptor. Neopterin autoinductive production can explain the amplificated neopterin release during activation of the cellular-mediated immune response (CMI), in spite of the decrease in the T helper cell subsets, which are the main gamma-IFN producers.
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PMID:Interleukin-2 and neopterin-induced neopterin release from peripheral blood mononuclear cells. 212 17

The cytokine profiles produced by peripheral blood mononuclear cell (PBMC) cultures were dependent upon the nature of the stimulus used. Powerful lymphocyte activators such as mitogens induced rapid cell proliferation together with the production of both inflammatory (IL-1 alpha, IL-1 beta, IL-6 and TNF alpha) and immune (IFN-gamma, TNF-alpha and TNF-beta) cytokines, and immune activation markers (soluble IL-2 receptor, neopterin and xanthopterin). Bacterial endotoxin failed to induce cell proliferation but resulted in the rapid production of inflammatory cytokines together with a short burst of IFN-gamma production, without the production of the other immune cytokines or activation markers. Alloantigen stimulation gave a typical immune cytokine and marker profile, with little or no production of inflammatory cytokines. Re-call antigens (candida and PPD) induced maximal cell proliferation at days 5 to 6, but induced little or no production of inflammatory cytokines. Markedly different immune cytokine profiles were obtained with these re-call antigens. Candida induced an early burst of IFN-gamma production on day 1 followed by later production of TNF-alpha. In cultures stimulated with PPD, both IFN-gamma and TNF-alpha were detected from day 2. With both re-call antigens, the levels of production of the activation markers were equivalent to the proliferative responses obtained.
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PMID:Stimulus-dependent production of cytokines and pterins by peripheral blood mononuclear cells. 762 84

Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.
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PMID:Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma. 785 83

High levels of the macrophage activation marker neopterin have been described in metastatic cancer patients. Since macrophages may either counteract or stimulate tumor development, it is important to establish which macrophage activity is mainly related to neopterin release. The present study was carried out to evaluate neopterin levels in metastatic solid tumor patients in respect with the antitumor macrophage cytokine TNF and with soluble IL-2 receptor (SIL-2R), whose secretion is stimulated by macrophages and it is associated with the immunosuppressive status of cancer patients. The study included 35 patients with metastatic solid neoplasms. Serum levels of neopterin, TNF and SIL-2R were measured in blood samples collected during the morning. Abnormally high concentrations of neopterin were seen in 18/35 (51%) patients. Patients with high levels of neopterin showed significantly higher concentrations of SIL-2R than those with normal neopterin values, whereas no difference was found in TNF levels. This study would suggest that the increased secretion of neopterin may reflect macrophage-mediated immunosuppression in metastatic solid neoplasms, rather than to be associated with the antitumor activity of macrophages.
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PMID:A study of interactions among markers of macrophage functions in metastatic solid tumors: neopterin levels in relation to those of tumor necrosis factor-alpha and of soluble interleukin-2 receptors. 797 92


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