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)

The effects of IL-10 on the generation of alloreactivity in primary mixed lymphocyte cultures (MLCs) were investigated. IL-10 inhibited in a dose-dependent fashion the alloantigen-induced proliferative responses. The suppressive effect was maximal when IL-10 was added at the beginning of the cultures, suggesting that it acts on the early stages of T cell activation. The proliferative responses were enhanced in the presence of a neutralizing anti-IL-10 mAb, indicating that endogenously produced IL-10 suppresses proliferation in primary MLC. The inhibitory effects of IL-10 were observed irrespective of whether irradiated allogeneic peripheral blood mononuclear cells, purified monocytes or freshly isolated B cells were used as stimulator cells. The proliferation of both the CD4+ and CD8+ T cell subsets was inhibited to a similar extent. The reduced proliferative responses were only minimally restored by high concentrations of exogenous IL-2, indicating that the effects of IL-10 are not exclusively due to inhibition of IL-2 synthesis. Furthermore, the production of IL-2, interferon (IFN)-gamma, IL-6, granulocyte macrophage colony stimulating factor, and tumor necrosis factor-alpha in primary MLCs was diminished by IL-10 and enhanced in the presence of anti-IL-10 mAb. The strongest effects were observed on the production of IFN-gamma. Although IL-10 reduces the proliferative responses, the ratios of CD3+CD4+ and CD3+CD8+ T cells remained the same in IL-10 treated and control cultures, yet the percentages of activated CD3+ T cells, as judged by CD25 and HLA-DR expression, were consistently reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin 10 inhibits allogeneic proliferative and cytotoxic T cell responses generated in primary mixed lymphocyte cultures. 128 62

The effects of Staphylococcus aureus enterotoxin A (SEA) and lipopolysaccharide (LPS) in cytokine production were assessed at the single cell level in cells obtained from healthy blood donors. Cytokine production was studied with UV-microscopy of fixed and permeabilized cells stained with cytokine specific monoclonal antibodies. The cytokines evaluated included tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-2, IL-4, interferon (IFN)-gamma and TNF-beta. LPS exhibited marked production of IL-1 alpha, IL-1 beta, TNF-alpha, IL-6 and IL-8. After LPS stimulation IL-1 alpha, IL-1 beta, TNF-alpha and IL-8 were the dominating products, all peaking at or before 4 hours after cell stimulation. In addition, IL-10 production was evident after 12 hours of cell stimulation. The T-lymphocyte-derived cytokines TNF-beta, IL-2, IFN-gamma and IL-4 were never detected in the cultures. All cytokine production, except IL-8, was downregulated at 96 hours. In contrast, peak production of IL-1 alpha, IL-1 beta and IL-8, which were the dominant products, occurred after 12 hours in the SEA-stimulated cultures. Further, a significant T-lymphocyte production of TNF-beta, TNF-alpha, IFN-gamma and IL-2 was found with peak production 12-48 hours after initiation. Only low amounts of IL-6 were evident. The two types of cytokine pattern and kinetics found may correspond to the different clinical conditions after invasive Gram-negative Escherichia coli vs Gram-positive Staphylococcus aureus infections in humans, with a much more rapid onset of disease after E. coli infections.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endotoxin and Staphylococcus aureus enterotoxin A induce different patterns of cytokines. 129 33

The effect of eosinophil cationic protein (ECP) upon proliferation of human B cell lines or purified B cells was studied. ECP inhibited proliferation of the human lymphoblastoid cell lines CBL and GM-1056 at doses of 0.1-5 ng/mL during 2-4 days of culture. The inhibitory effect of ECP was reversible and not due to toxic damage. Moreover, inhibition could be blocked by anti-ECP serum while the control serum failed to do so. Of various cytokines tested--including interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6; interferon (IFN)-alpha or IFN-gamma--IL-4 reduced the inhibition, while other cytokines failed to do so. The reduction of inhibition was specific to IL-4 since reduction by IL-4 was blocked by anti-IL-4 antibody but not by the control antibody. ECP also inhibited proliferation of tonsillar small resting B cells stimulated with anti-mu antibody plus low molecular weight B-cell growth factor (BCGF) or of large activated B cells. In contrast, ECP had no effect on proliferation of unstimulated small resting B cells. This inhibition was also reduced by IL-4 specifically. These results indicate that ECP may also act as a B-cell regulating factor.
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PMID:Human B-cell growth-inhibitory activity of eosinophil cationic protein. 130 27

The metastatic non-small cell lung cancer (NSCLC) still remains an untreatable disease, and the role played by chemotherapy has yet to be defined. The new immunotherapeutic strategies, such as interferon and IL-2, seem to be also less effective, since they generally determine only a stabilisation of disease. On the basis of previous experimental results suggesting a synergistic action between IL-2 and the pineal neurohormone melatonin (MLT), a study was started to evaluate the clinical efficacy and toxicity of a neuroimmunotherapeutic combination consisting of IL-2 plus MLT as a first line therapy in metastatic NSCLC. The study included 20 patients (adenocarcinoma: 10; epidermoid cell carcinoma: 7; large cell carcinoma: 3). MLT was given orally at a dose of 10 mg day-1 at 8.00 pm every day, starting 7 days before the onset of IL-2 administration. IL-2 was given subcutaneously at a dose of 3 x 10(6) IU m-2 every 12 h for 5 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In responder patients or in those with stable disease, a second cycle was given after a rest-period of 21 days. A partial response was achieved in 4/20 (20%) patients. Ten other patients had a stable disease (50%), whereas the last six patients progressed. Toxicity was low in all cases. This study shows that the neuroimmunotherapeutic therapy with IL-2 and the pineal hormone MLT may represent a new effective and well tolerated treatment in metastatic NSCLC, with results comparable to those obtained with chemotherapy, but with an apparent lower biological toxicity.
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PMID:Biological and clinical results of a neuroimmunotherapy with interleukin-2 and the pineal hormone melatonin as a first line treatment in advanced non-small cell lung cancer. 132 55

In asthma, a beta-adrenoceptor dysfunction may be the consequence of an active disease state rather than a fundamental abnormality. In the present study the possible involvement of T lymphocytes in beta-adrenergic impairment was investigated by studying the effects of lymphocyte-derived mediators of beta-adrenoceptor function of human peripheral blood mononuclear cells (PBMCs) and guinea pig trachea. Supernatants of phytohemagglutinin- or concanavalin A-activated PBMCs from either persons with asthma or healthy persons inhibited isoprenaline stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production of PBMCs after 20 hours of preincubation. These supernatants also inhibited beta-adrenoceptor function of PBMCs from patients with asthma to the same extent. The isoprenaline stimulated cAMP production of PBMCs was not altered after a 2-hour preincubation period with human interleukin-1 (IL-1), IL-2, IL-3, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN-gamma). In contrast, after 20 hours of preincubation, stimulated cAMP production of PBMCs was significantly diminished, with 63% by IL-1 (40 U/ml, p less than 0.01), with 36% by IL-2 (100 U/ml, p less than 0.05), with 37% by IFN-gamma (1000 U/ml, p less than 0.05), and with 21% by GM-CSF (100 U/ml, p less than 0.05). Preincubation of guinea pig tracheal segments with IL-1, IL-2, IL-4, or GM-CSF during 1 or 3 days did not affect the EC50 values or the maximal relaxation of isoprenaline dose response curves.
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PMID:Effects of cytokines on beta-adrenoceptor function of human peripheral blood mononuclear cells and guinea pig trachea. 132 72

It was recently observed that treatment of patients with a high dosage of human interleukin (IL-2) resulted in suppression of plasma concentrations of testosterone. A murine model was developed to assess the direct and indirect effects of murine IL-2 and the secondarily released cytokines, gamma interferon (INF gamma), and tumor necrosis factor (TNF alpha), on testosterone production in isolated Leydig cells. Pretreatment for 24 hours with IL-2 (100 to 500 IU/ml) or INF gamma (100 to 1000 IU/ml) significantly decreased testosterone production in response to luteinizing hormone (LH; P < 0.02 and 0.005, respectively). The combinations of INF gamma with either TNF alpha or IL-2 produced enhanced suppressive effects on Leydig cell testosterone production. Steroidogenic precursors (22-hydroxycholesterol, 17 alpha-hydroxypregnenolone, and dehydroepiandrosterone) restored testosterone secretion to control levels after preincubation with INF gamma or TNF alpha. In contrast, the inhibition of testosterone synthesis produced by either IL-2 or INF gamma plus TNF alpha could be reversed by 17 alpha-hydroxypregnenolone and dehydroepiandrosterone, but not by 22-hydroxycholesterol (P < 0.01). Dibutyryl cyclic adenosine monophosphate was also ineffective in reversing the inhibitory effects of these cytokines on synthesis. Although IL-2 directly inhibited synthesis in isolated Leydig cells, it stimulated testosterone production (P < 0.005) in minced murine testes. This suggests that IL-2 releases regulatory factors from other cells that were able to overcome the direct inhibitory effect of IL-2. This stimulatory effect was not caused by INF gamma and TNF alpha because INF gamma alone or with TNF alpha inhibited (P < 0.005) testosterone production in minced testes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Direct and indirect effects of murine interleukin-2, gamma interferon, and tumor necrosis factor on testosterone synthesis in mouse Leydig cells. 133 Oct 12

Basophil chemotactic activity (BCA) of eight recombinant human (rh) cytokines was examined. Highly purified basophils were obtained by Percoll discontinuous gradients, followed by negative selection using flow cytometry. Then BCA was measured by means of modified Boyden chamber method. Both interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) had much more potent BCA than complement C5a, leukotriene B4 and platelet activating factor, well known as granulocyte chemotactic factors. Chemotaxis rather than chemokinesis was shown in chequerboard analysis of basophil migration induced by IL-3 and GM-CSF. Relatively high concentrations of IL-5 also induced basophil migration, although predominantly chemokinetic. IL-8 had apparent BCA, which was not so high as that of C5a. In contrast, IL-2, IL-4, interferon(IFN)-gamma and granulocyte colony-stimulating factor (G-CSF) had no significant BCA. These findings suggest that IL-3, IL-5, GM-CSF and, perhaps, IL-8 have an effect on basophil migration as well as modulation of basophil mediator release and may provide some insight into the basophil accumulation observed in late-phase allergic responses.
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PMID:Effects of cytokines on human basophil chemotaxis. 133 81

The modulation of adhesion molecules on human large granular lymphocytes (LGL) by interleukin (IL)-2 was investigated both in vivo and in vitro. Intercellular adhesion molecule-1 (ICAM-1; CD54) expression increased on LGL of cancer patients receiving IL-2 adoptive immunotherapy. ICAM-1 expression on LGL isolated by Percoll gradient centrifugation, LGL purified, and expanded by adherence to plastic surfaces and LGL identified by Leu 19 (CD56) monoclonal antibody were increased significantly in response to IL-2 in vitro. Exposure of LGL to IL-1, interferon (IFN)-gamma, and tumor necrosis factor (TNF) in vitro did not induce ICAM-1. The expression of LFA-1 (CD11a/CD18), a receptor for ICAM-1, and other leukocyte adhesion molecules, including Mac-1 (CD11b/CD18) and p150,95 (CD11c/CD18), was only maintained by IL-2. IL-2 induction of ICAM-1 and the maintenance of CD18 complex expression on small lymphocytes separated by Percoll gradients were similar to that on LGL. We conclude that IL-2 enhances the expression of ICAM-1 on multiple human lymphocyte populations including LGL effectors. Expression of the CD18 complex on LGL does not appear to be highly regulated by IL-2. These findings may have implications relevant to the role of these adhesion molecules in the activities of LGL modulated by IL-2.
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PMID:Modulation of adhesion molecules on human large granular lymphocytes by interleukin-2 in vivo and in vitro. 134 85

We have examined the regulation of interleukin (IL)-4 production by human peripheral blood T cells. Production of IL-4 was shown to be regulated differently from IL-2 and interferon(IFN)-gamma production. Stimulation of peripheral blood lymphocytes with anti-CD3, anti-CD2, anti-CD28, Phorbol 12-myristate 13-acetate (PMA) or IL-2 as a single stimulant did not induce IL-4 production. However, combinations of anti-CD2 with either anti-CD28 or IL-2 resulted in IL-4 production, peaking at days 3-4. Stimulation with anti-CD3 instead of anti-CD2 gave similar results, but was less potent. After days 3-4, IL-4 levels decreased, most likely due to consumption of IL-4. PMA profoundly affected cytokine production, it enhanced IL-2 production by at least tenfold, whereas, in the same cell population, IL-4 production was almost completely inhibited. This was observed at the protein as well as at the mRNA level. In contrast, agents that increase intracellular cAMP levels inhibited IL-2 production but left IL-4 production unaffected. IFN-gamma production behaved similar to IL-2 production but the effects were less outspoken.
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PMID:Interleukin (IL)-4 production by human T cells: differential regulation of IL-4 vs. IL-2 production. 134 33

The cytokine secretion profiles of T cell lines (TCL) specific for purified protein derivative (PPD) or streptokinase (SK), contemporarily derived from nine atopic and nine nonatopic individuals, were compared. Upon stimulation with phorbol myristate acetate (PMA) plus anti-CD3 monoclonal antibody (mAb), all TCL from both atopics and nonatopics produced interleukin (IL)-2 and interferon (IFN)-gamma. The mean IL-2 production by PPD- or SK-specific TCL from both atopics and nonatopics was similar, whereas the mean IFN-gamma production by TCL derived from atopics was significantly lower. In addition, both PPD- and SK-specific TCL from atopics produced detectable amounts of IL-4 and IL-5, whereas the corresponding TCL derived from nonatopics did not. A total number of 107 and 99 PPD-specific CD4+ T cell clones (TCC) were then derived from TCL of 4 atopic and 4 nonatopic donors and assessed for their profile of cytokine production in response to stimulation with either PMA plus anti-CD3 mAb or the specific antigen. Under both these experimental conditions, virtually all PPD-specific TCC from both atopic and nonatopic individuals produced IL-2 and IFN-gamma. In contrast, the great majority of PPD-specific TCC derived from nonatopic individuals did not produce IL-4 and IL-5, whereas high proportions of PPD-specific TCC derived from atopic donors displayed the ability to produce noticeable amounts of IL-4 and IL-5 besides IL-2 and IFN-gamma. These data indicate that CD4+ T cells from atopic individuals are able to produce IL-4 and IL-5 in response to bacterial antigens, such as PPD and SK, that usually evoke responses with a restricted type-1 T helper (Th1)-like cytokine profile in nonatopic individuals. Aberrant IL-4 production by Th cells may represent one of the immune alterations responsible for enhanced IgE antibody production in atopic people.
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PMID:Aberrant interleukin (IL)-4 and IL-5 production in vitro by CD4+ helper T cells from atopic subjects. 135 Sep 83


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