Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:BIOD00082 (IL-2)
 29,198 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies further investigate the immunoenhancement properties of UDMH by utilizing Corynebacterium parvum-induced immunosuppressed mice as well as evaluating activated macrophage production of reactive oxygen intermediates or their effects. Forty-eight hour Con A-induced lymphoblastogenic responses from splenocytes isolated from C. parvum and UDMH-treated Balb/C mice were significantly increased compared with C. parvum alone, although less than normal control mice (no treatment). In vitro bioassay of IL-2 production in cell culture supernatant isolated from these same treatment groups exhibited a pattern of stimulation similar to that of lymphocyte blastogenesis. In addition, UDMH did not interfere with H2O2-mediated suppression of either Con A- or LPS-induced lymphocyte blastogenesis and actually enhanced suppression of Con A-induced lymphocyte cultures at 25 micrograms/ml. We also report that production of superoxide anion from TPA-activated peritoneal macrophages exposed to various concentrations of UDMH in vitro was not affected. Although in vivo exposure to UDMH partially reversed C. parvum-induced immunosuppression in mice, the exact mechanism by which UDMH acts to reverse this immune suppression is not clear. UDMH does not appear to interfere with either activated peritoneal macrophage production of superoxide anion or H2O2-induced suppression of lymphocyte blastogenesis to elicit immune enhancement.
 ...
PMID:Effect of 1,1-dimethylhydrazine (UDMH) on Corynebacterium parvum-associated immunosuppression in mice. 131 18

We studied the differential effects of polymorphonuclear leukocyte (PMN) secretion on human natural killer cells (NK) and lymphokine-activated killer cell (LAK) activity. Supernatant fluids from PMN stimulated by serum-opsonized zymosan (SOZ), n-formylmethionylleucylphenylalanine (FMLP) and interleukin-8 (IL-8) were incubated with peripheral blood lymphocytes (PBL) for 1 d and 4 d. Supernates from unstimulated PMN and PMN induced by FMLP and IL-8 decreased NK and LAK cytotoxicity in a dose-dependent fashion against K562 and M14 targets, respectively. Only the suppression caused by supernates from unstimulated PMN was ablated by incubation of PMN with indomethacin. Secretions from PMN stimulated by SOZ increased both NK and LAK cytotoxicity and induced PBL proliferation synergistically with IL-2. This enhancing factor was heat-labile, nondialyzable (MWCO 3500), and not blocked by anti-interferon-gamma. Anaerobic conditions did not influence the modulatory activity of PMN supernates, indicating that oxygen metabolites were not involved. We conclude that PMN release factors that modulate in vitro NK and LAK activities.
 ...
PMID:The differential effects of polymorphonuclear leukocyte secretion on human natural killer cell activity. 152 37

The requirements for activation of anti-mycobacterial and anti-listerial activity of human monocytes were investigated. Human monocytes could be activated to display enhanced anti-mycobacterial activity by a 24-h treatment with lipopolysaccharide. The mediator induced by this treatment was identified as being tumour necrosis factor-alpha (TNF-alpha). Addition of recombinant TNF-alpha (rTNF-alpha) to the cultures of human monocytes for 24 h yielded comparable results (minimal dose required for induction of anti-mycobacterial activity, 10 U ml). Addition of anti-TNF-alpha antibody completely abrogated the effect. A similar treatment protocol failed to activate enhanced anti-listerial activity. To trigger anti-listerial activity, sequential treatment of human monocytes with rTNF-alpha and IL-2 was required. Treatment of monocytes with 10 U ml rTNF-alpha for 24 h followed by incubation in the presence of 200 U/ml of IL-2 for an additional 24 h yielded a reduction of listerial growth which was moderate but statistically significant (P less than 0.001). The activation of monocytes observed with rTNF-alpha/IL-2 treatment was (i) dependent on both cytokines; (ii) sequence dependent (i.e. when IL-2 was added prior to rTNF-alpha, no effect was observed); and (iii) absent in cells treated with one cytokine only. Enhancement of anti-listerial activity by sequential use of cytokines was not accompanied by an increase in oxidative burst, which indicated that oxidative mechanisms were not the reason for the observed Listeria monocytogenes growth restriction. Further support for this hypothesis was obtained after interferon-gamma treatment of human monocytes which led to an augmented PMA-inducible release of active oxygen radicals, but was not paralleled by growth restriction of L. monocytogenes. Our results indicate that TNF-alpha plays a crucial role in the activation of monocytes for growth restriction of intracellular microbes. Activation of human monocytes to restrict the growth of the facultative intracellular bacteria Mycobacterium avium intracellulare and L. monocytogenes, however, follows different patterns, the initial trigger in both cases being provided by TNF-alpha-induced signals.
 ...
PMID:Induction of anti-mycobacterial and anti-listerial activity of human monocytes requires different activation signals. 164 23

Ferric ammonium citrate (FAC) is nonmitogenic for human peripheral blood mononuclear cells (PBM) but has a potent mitogenic activity in the presence of IL-2. FAC in the presence of IL-2 increases the number of human peripheral blood mononuclear cells (PBM) expressing receptors for IL-2 and transferrin. FAC also markedly stimulates human PBM treated with supraoptimal, nonmitogenic concentrations of Con A. FAC, in the presence of IL-2, is a T-cell mitogen with a stringent requirement for macrophages. FAC stimulates the production of TNF-alpha and IFN-gamma in human PBM, and this effect is potentiated by IL-2. Thiourea and 3-amino-1,2,4-triazole selectively inhibit mitogenesis induced by FAC, indicating that oxygen radicals or peroxidase may mediate the triggering signal induced by this mitogen. In addition to hemin, as we have previously reported, and FAC, a variety of iron-containing proteins have lymphocyte stimulatory properties in combination with IL-2. They include horseradish peroxidase, cytochrome c, myoglobin, and transferrin. We have given the name ferro-mitogens to this group of compounds.
 ...
PMID:Ferro-mitogens: iron-containing compounds with lymphocyte-stimulatory properties. 201 30

The antithyroid drugs methimazole and propylthiouracil have been shown to affect the function of monocytes and B and T lymphocytes in vitro. The aim of this study was to investigate the mechanism responsible for signalling between these various cell types. Propranolol, a drug known to have no effect on the immune system, was also included as a control against which the effects of the other drugs could be monitored. Peripheral blood lymphocytes from control subjects were stimulated with phytohemagglutinin in the presence or absence of antithyroid drugs. Propranolol was found significantly to inhibit beta 2 microglobulin production. In addition it was also found to be a very weak scavenger of free oxygen radicals. Methimazole significantly increased interleukin 2 levels (p less than 0.01), but had no significant effect on either gamma-interferon or beta 2 microglobulin production. Propylthiouracil also increased interleukin 2 levels (p less than 0.001) and significantly decreased beta 2 microglobulin production (p less than 0.01). Both drugs were found to be scavengers of free O2 radicals. It would appear that IL-2 is involved in intercellular signalling and this process may involve free radicals.
 ...
PMID:The effects of antithyroid drugs on intercellular mediators. 211 14

Subjects with Down syndrome (DS) have a high mortality due to infections and a high risk of developing malignancies. These observations, together with the demonstration of a frequent occurrence of HBsAg carrier state and of autoantibodies, have prompted investigations of the immune function in DS. Thymic morphological and functional abnormalities have been demonstrated. Peripheral blood mononuclear cells of DS subjects have been shown to include a high number of T lymphocytes with low avidity for sheep erythrocytes and a very high percentage of cells with an NK phenotype. However, NK activity is low in DS. Production of some important cytokines, such as IL-2, is depressed, thus contributing to T-cell derangement. Abnormalities of the B-cell compartment were also demonstrated, with a tendency towards high IgG and low IgM serum levels. Controversial results have been obtained with regard to antigen-specific antibody response. Also phagocytes of DS subjects display some characteristic functional impairments, with low chemotactic ability and reduced production of oxygen radicals. Despite the clearly established and rather detailed evidence of immune derangements, therapeutic trials have been anecdotal and resulted in marginal effects. HBV vaccination is highly advisable in DS because of the high risk of becoming chronic HBV carriers once infected.
 ...
PMID:Immunology of Down syndrome: a review. 214 49

Interleukin (IL)-2 therapy leads to respiratory dysfunction due to increased vascular permeability. This study examines the role of the chemoattractant, immunomodulator, and permeability-promoting agent leukotriene (LT) B4 in this setting. Sheep with chronic lung lymph fistulae were given IL-2, 10(5) U/kg as an IV bolus (n = 6). Within 2 hours this led to a significant increase in LTB4 levels in both plasma and lung lymph. The mean pulmonary artery pressure (MPAP) rose while the pulmonary artery wedge pressure was unchanged. Arterial oxygen tension (PaO2) fell. Lung lymph flow (QL) was tripled (P less than 0.05) at 3 hours, coinciding with an increase in the lymph/plasma (L/P) protein ratio (P less than 0.05) resulting in an increase in the lymph protein clearance (P less than 0.05), data documenting increased microvascular permeability to protein. Mild leukopenia and thrombocytopenia (P less than 0.05) occurred. Body temperature rose and shaking chills were common. Pretreatment with the lipoxygenase inhibitor diethylcarbamazine (DEC; n = 6) reduced baseline plasma LTB4 levels and prevented the IL-2-induced increases in LTB4 in plasma and lung lymph (P less than 0.05). In contrast to IL-2 treatment alone, DEC blunted the increase in MPAP and prevented the rises in QL (P less than 0.05), L/P protein ratio (P less than 0.05), and lymph protein clearance (P less than 0.05). DEC also prevented the IL-2-induced leukopenia, the fall in platelet count, and the rise in body temperature (P less than 0.05, respectively). Infusion of IL-2 excipient control (n = 5) did not affect plasma or lymph LTB4 levels but there were mild increases in MPAP (P less than 0.05). The QL also rose but this occurred while the L/P protein ratio fell (P less than 0.05). Body temperature rose moderately. The PaO2, leukocyte, and platelet counts were unaffected. These data indicate that IL-2 administration leads to pulmonary dysfunction manifest by pulmonary hypertension and increased vascular permeability, events associated with LTB4 synthesis and prevented by DEC. Leukotriene B4 appears therefore to mediate the IL-2-induced lung injury.
 ...
PMID:Interleukin-2-induced lung permeability is mediated by leukotriene B4. 217 70

Activated polymorphonuclear neutrophilic granulocytes (PMN) play an important role in propagation of inflammatory reactions and are capable of mediating tissue damage particularly by release of reactive oxygen species and lysosomal contents. Cytokines produced by monocytes as well as epidermal cells were recently shown to modulate PMN function. Therefore, the effect of immunomodulating cytokines on the oxidative metabolism of isolated human PMN was tested by functional as well as ultrastructural criteria. The following recombinant human cytokines were tested: tumor necrosis factor (TNF alpha), lymphotoxin (TNF beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, G-CSF, PDGF, TGF-beta, interleukin-1 (IL-1) alpha and beta, IL-2, IL-3, IL-4, IL-5, IL-6, MONAP/MOC/NAF (IL-8), interferon-alpha and -gamma. Only TNF alpha, TNF beta and GM-CSF were found to be direct stimuli of the oxidative burst in human PMN whereas IL-3, IL-5, and IL-8 were active only at extremely high concentrations. None of the other cytokines tested induced any significant effect on isolated human PMN at physiological concentrations. The results clearly demonstrate that only selected cytokines are capable of inducing a long lasting activation of PMN oxidative metabolism. Release of these mediators represents a specific signal for PMN activation in inflammatory disease states.
 ...
PMID:Activation of the oxidative metabolism in human polymorphonuclear neutrophilic granulocytes: the role of immuno-modulating cytokines. 225 41

Patients with chronic renal insufficiency under maintenance dialysis present numerous immunological alterations to which renal impairment, nutritional disturbances, blood transfusions and biocompatibility of the dialysis system may contribute. Although presently less frequent, infections still represent an important source of mortality and morbidity. Polynuclear neutrophils chemotactic responses are decreased and bactericidal capacity reduced, especially in polytransfused patients with iron overload. Lymphocyte counts are diminished and T lymphocytes present several alterations, including defective IL-2 synthesis, spontaneous expression of the p55 (CD25) chain of IL-2 receptor with high serum levels of this molecule, and defective T helper function in antibody production. Such alterations may account for the defect of delayed hypersensitivity reactions and the diminished antibody response after vaccination. Complement activation, increased expression of adhesion molecules by leukocytes, production of IL-1 and reduced oxygen molecular species during dialysis might contribute to immunological disorders of these patients.
 ...
PMID:[Immune deficits in hemodialysis patients]. 232 86

We analyzed the haemodynamic effects of high doses of r-Met Hu IL-2 [ala-125] in four patients with advanced cancer. Haemodynamic parameters were measured daily from days 1 to 6 of treatment. Mean arterial pressure decreased significantly (98 +/- 11 mmHg on day 1 versus 84 +/- 7 mmHg on day 5; p = 0.0435) as did systemic vascular resistance (2042 +/- 296 dynes s cm-5 m-2 on day 1 versus 1166 +/- 87 dynes s cm-5 m-2 on day 5; p = 0.003). There was a significant increase in mean pulmonary artery pressure (13.25 +/- 3.30 mmHg on day 1 versus 20.75 +/- 7.41 mmHg on day 5; p = 0.03), systemic oxygen consumption (173.5 +/- 37.8 ml min-1 m-2 on day 1 versus 257.8 +/- 20.5 ml min-1 m-2 on day 5; p = 0.02) and cardiac index (3.86 +/- 0.58 l min-1 m-2 on day 1 versus 5.77 +/- 0.21 l min-1 m-2 on day 5; p = 0.008). There was no significant decrease in the arteriovenous oxygen content difference (4.5 +/- 0.8 ml dl-1 on day 1 versus 4.46 +/- 0.22 ml dl-1 on day 5). Increases in oxygen delivery (570 +/- 163 ml min-1 m-2 on day 1 versus 750 +/- 109 ml min-1 m-2 on day 5 and oxygen extraction ratio (29.95% +/- 6.37% on day 1 versus 34.60% +/- 4.35% on day 5) were not statistically significant. We concluded that the haemodynamic effect induced by high doses of r Hu-IL-2 is similar to that seen in septic shock.
 ...
PMID:Haemodynamic effects induced by intravenous administration of high doses of r-Met Hu IL-2 [ala-125] in patients with advanced cancer. 235 78


1 2 3 4 5 6 7 8 9 10 Next >>