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)

We have treated 18 patients with metastatic malignant melanoma (MM) with high-dose IL-2 administered by continuous iv infusion in combination with dacarbazine (DTIC), and correlated the clinical response with various hematologic and immunologic parameters. Two regimens differing in the sequence of treatment were employed, and 1-6 treatment cycles were given, depending on patient response. Two patients had a complete response (CR, 46+m, 14m), two patients a partial response (PR, 16m,6m), one a minimal response and four had a stable disease lasting 2-7 months, thus the response rate (CR+PR) was 22%. None of the following parameters, tested prior to initiation of the therapy and 1-2 days after termination of each course of IL-2, correlated with the clinical response: WBC counts (total and differential), levels of blood CD4 and CD8 T cells, NK cells, monocytes and B cells, production of IL-1 and IL-1 inhibitor by monocytes, responsiveness to 3 mitogens, NK/LAK cell activity, and serum levels of IL-1 alpha, IL-2, soluble IL-2 receptor, and TNF alpha. The only prognostic parameter was the greater increase in the level of IL-2 receptor (Tac)-bearing lymphocytes in the responding patients after 1-3 cycles of IL-2. The data suggests that non-specific immune parameters have no prognostic value for patients undergoing IL-2-based immunotherapy.
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PMID:Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response. 144 17

Thymic epithelial cells (TEC) are known to secrete thymic hormones that influence maturation of T lymphocytes. One of these peptides, thymulin, requires zinc in an equimolar ratio for biological activity. A previous study [Cousins, R. J. & Leinart, A. S. (1988) FASEB J. 2, 2884-2890] showed that interleukin 1 (IL-1) in vivo stimulates zinc uptake by the thymus. Both the alpha and beta forms of IL-1, which stimulate proliferation of human TEC, also stimulate their uptake of zinc in vitro, and this latter stimulation is both dependent and independent of proliferation. Zinc induces zinc accumulation without proliferation. Two other stimulants of proliferation, bovine pituitary extract and epidermal growth factor, stimulate zinc uptake by TEC, but only in a manner dependent on proliferation. Utilizing in situ hybridization, we show that the IL-1 alpha and beta forms and zinc induce metallothionein mRNA expression TEC. Metallothionein is thought to be involved in the transfer of zinc to thymulin. IL-1 was shown to stimulate the secretion of thymulin as measured both by its ability to stimulate induction of IL-2 receptor-positive lymphocytes from human peripheral blood lymphocytes and by the azathioprine-sensitive rosette assay. In addition, the zinc-thymulin complex in the presence, but not absence, of IL-1 stimulates nuclear protein kinase C in isolated lymphocyte nuclei. IL-1 apparently regulates the synthesis or secretion and delivery of zinc-thymulin complex to the T-lymphocyte system.
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PMID:Interleukin 1 regulates secretion of zinc-thymulin by human thymic epithelial cells and its action on T-lymphocyte proliferation and nuclear protein kinase C. 150 95

EL 4-6.1 cells, variants of the murine EL4 thymoma cell line, can be activated by interleukin 1 (IL-1) or phorbol 12-myristate-13-acetate (PMA), or PMA+IL-1 to secrete interleukin 2 (IL-2) and interleukin 4 (IL-4) and to express the IL-2 receptor (IL-2R). To compare the different activation pathways, we examined the effects of staurosporine (STAR) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), two protein kinase C (PKC) inhibitors, on the induction of interleukin secretion and IL-2R expression in these cells. We report here that nanomolar concentrations of STAR strongly potentiated (20- to 30-fold) the production of IL-2 or IL-4, when EL 4-6.1 cells were induced by IL-1 alpha (or IL-1 beta) alone. By contrast, at identical concentrations, STAR dose-dependently inhibited the production of IL-2 and IL-4 resulting from PMA or PMA+IL-1 cell treatment. STAR also negatively affected the expression of IL-2R, which was dependent on PMA-sensitive PKC with either IL-1, PMA, or PMA+IL-1 stimulation. The changes in interleukin production and IL-2R expression in EL 4-6.1 activated cells were correlated with changes at the mRNA level measured by quantitative polymerase chain reaction (PCR). This finding suggests a pretranslational effect of the drug. At micromolar concentrations, H7 showed the same effects as STAR, but only increased IL-1-triggered interleukin secretions twofold. We observed that the action of PKC inhibitors did not result from modification of IL-1 receptor (IL-1R) expression in EL 4-6.1 cells. Thus, our data show that PKC inhibitors clearly distinguish between IL-1 and PMA stimulatory pathways. In addition, they suggest that the IL-1 stimulatory pathway involves PKC(s) [or other undefined kinase(s)] which regulate this pathway and differ from PKC(s) activated by PMA.
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PMID:Contrasting effects of the protein kinase C inhibitor staurosporine on the interleukin-1 and phorbol ester activation pathways in the EL4-6.1 thymoma cell line. 156 50

Serum cytokine profiles were evaluated in immunized and nonimmunized human volunteers after challenge with infectious Plasmodium falciparum sporozoites. Three volunteers had been immunized with x-irradiated sporozoites and were fully protected from infection. Four nonimmune volunteers all developed symptomatic infection at which time they were treated. Sera from all volunteers were collected at approximately 20 time points during the 28-d challenge period; levels of IL-1 alpha, IL-1 beta, IL-2, IFN-gamma, tumor necrosis factor-alpha, IL-4, IL-6, granulocyte macrophage-colony-stimulating factor, and soluble CD4, CD8, and IL-2 receptor (sCD4, sCD8, and sIL-2R, respectively) were determined by ELISA. C-reactive protein (CRP) was assayed by radial immunodiffusion. Parasitemic subjects developed increases in CRP and IFN-gamma, with less marked increases in sIL-2R and sCD8; the other cytokines tested did not change. CRP increases were abrupt and occurred at the onset of fever (day 14 after challenge). IFN-gamma increases were also abrupt, preceding those of fever and CRP by one day. Increases in sIL-2R and sCD8 were more gradual. Increases in fever, CRP, IFN-gamma, and sCD8 were concordant in each volunteer. Early IL-6 increases were noted in the protected vaccinees. Thus, after challenge with virulent P. falciparum, unique systemic cytokine profiles were detectable both in immunized, nonparasitemic volunteers and in unvaccinated, parasitemic subjects. The contrasting cytokine profiles in the two groups may relate to mechanisms of protection and immunopathology in experimental human malaria.
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PMID:Serum cytokine profiles in experimental human malaria. Relationship to protection and disease course after challenge. 164 22

Nickel is the major cause of metal-induced allergic dermatitis. Twelve nickel-specific T cell clones were used to investigate the cellular immune reactions occurring in nickel sensitivity. The selection between the alternative T cell receptors alpha beta and gamma delta and two alternative V beta genes (V beta 5 and V beta 8) were studied to see if nickel induces a selective pressure for clones bearing particular genes. Cell surface markers were studied by monoclonal antibodies and flow cytometry. Soluble mediators were measured by an ELISA method. The clones used T cell receptor alpha beta genes but did not use V beta 5 or V beta 8. They were T helper clones with a primed memory marker (CD3+ CD4+ CD8- CD45RO+) and carried HLA-DR. None of the clones secreted IL-1 alpha, all of them secreted IL-2 receptor. Four clones secreted IL-1 beta, six IL-4 and seven IL-6, the peaks in IL-2R and IL-6 secretion preceding IL-4 secretion. The clones helped immunoglobulin synthesis. The clones from late effector phase of the nickel allergic reaction favours the use of T cell receptors alpha beta genes. Nickel-specific clones were phenotypically indistinguishable but differed in soluble mediators produced.
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PMID:Characterization of nickel-specific T cell clones. 182 95

Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and soluble IL-2 receptor (sIL-2R) serum levels were evaluated in 24 hairy cell leukemia (HCL) patients. Of these, three patients were studied at the time of diagnosis, 12 in relapse after interferon (IFN) therapy, eight with a partial response after IFN and one with a complete response after 2-deoxycoformycin (DCF) therapy. Statistically significant differences were observed in the serum levels of IL-1 beta and sIL-2R between HCL patients and controls. These were 400.3 pg per 0.1 ml (range 23.2-990) and 64.3 pg per 0.1 ml (20-115) for IL-1 beta and 4667.2 U/ml (488-7800) and 424.3 U/ml (188-666) for sIL-2R, respectively. In contrast, IL-1 alpha measurements showed no statistical differences between the two groups. A significant increase of sIL-2R (p = 0.01) and IL-1 beta (p = 0.03) serum levels was observed in patients studied at the time of diagnosis or in relapse compared to those in partial or complete remission. IL-1 beta serum levels directly correlated with sIL-2R (p less than 0.0001) and with hairy cell (HC) bone marrow infiltration, expressed by the HC index (p = 0.003). The comparison of IL-1 beta serum levels of HCL patients with those detected among 149 patients grouped according to diagnosis (Hodgkin's disease = 17, non-Hodgkin's lymphomas = 57, acute non-lymphoid leukemia = 46, and acute lymphoid leukemia = 29) indicate that HCL patients showed the highest IL-1 beta serum level increase, indicating that IL-1 beta could be used as a specific clinical marker of this disease.
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PMID:Serum interleukin-1 beta levels correlate with neoplastic bulk in hairy cell leukemia. 207 45

We investigated the induction of tissue factor by lymphokines in human monoblastic leukemia cell lines (U937) and leukemic cells from AML (acute myelogenous leukemia) patients. After incubation for 24 h, IL-2 enhanced the intracellular tissue factor 15-fold with U937 cells, and GM-CSF enhanced it 6-fold. In contrast, other lymphokines, such as IL-1-alpha, IL-1-beta, IL-3, IL-4 and G-CSF, did not affect the activity of tissue factor. The leukemic blasts, depleted of T-lymphocytes, taken from five out of 16 AML patients showed a 2.5-14-fold increase in the activity of tissue factor per cell following incubation with 200 u/ml of IL-2 for 72 h. The IL-2 induced tissue factor activity more markedly than GM-CSF. Tissue factor stimulation by IL-2 did not correlate with the expression of the IL-2 receptor, Tac, but correlated well with FAB classification of AML cells. IL-2 responders were found in M4 and M5 subtypes only, but not all M4/M5 leukemias responded to IL-2. These findings indicate that IL-2 can mediate the tissue factor induction in the monocytic type of AML and the effect is not mediated by Tac receptors. This may shed a new light on our understanding of hypercoagulability in acute monoblastic leukemia.
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PMID:Induction of tissue factor by interleukin-2 in acute myelogenous leukemia (AML) cells. 208 39

The regulation of rat lymphokine-activated killer (LAK) cell generation from their purified precursors using various cytokines was studied. Several important findings emerged from this study. These include: (i) interleukin-2 (IL-2), but not any other cytokine tested, is pivotal for the development of LAK cells; (ii) transforming growth factor beta 1 (TGF-beta) inhibits IL-2-induced LAK cell differentiation, but not proliferation, regardless of the dose of IL-2 used; (iii) interferon-gamma (IFN-alpha) is inhibitory for LAK cell proliferation, but not differentiation; (iv) tumour necrosis factor-alpha (TNF-alpha) or IFN-gamma synergize with a low but not a high concentration of IL-2; (v) TNF-alpha reverses the anti-differentiative activity of TGF-beta 1 in the presence of a high, but not a low, concentration of IL-2; (vi) anti-p55 IL-2 receptor (R) is not inhibitory for LAK cell development but, on the contrary, a low concentration of this antibody synergizes with IL-2; (vii) IL-1 alpha, IL-1 beta, IL-3, IL-4, IL-6, IFN-alpha. TNF-alpha, or TGF-beta 1 do not affect LAK cell function; and (viii) IL-2 may provide two separate signals for LAK precursors: one is proliferative and the other is differentiative.
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PMID:Differential effects of various cytokines on the generation of rat LAK cells from their purified precursors. 211 78

Our laboratory analyzed the expression of lymphokine and cytokine mRNA in CD3- peripheral blood large granular lymphocytes (LGL). Herein we present evidence that this subset of lymphocytes can synthesize IL-1 beta mRNA constitutively and that the cytoplasmic mRNA levels of IL-1 beta can be increased rapidly by interleukin (IL)-2. IL-1 alpha mRNA is expressed constitutively very infrequently and increases in IL-1 alpha mRNA are seen only after prolonged incubation with IL-2. Furthermore, IL-1 activity could not be detected in LGL culture supernatants, indicating that other processes may be involved in releasing biologically active IL-1 from LGL. In addition, MAb to the p75 IL-2 receptor on LGL abrogated IL-2 induction of IL-1 beta mRNA, suggesting that IL-2 signaling via the p75 IL-2 receptor induced IL-1 beta gene expression in LGL. Since, in contrast to T cells, LGL are capable of mediating effector functions without prior stimulation, they are said to be already "primed" for response. Overall, these data suggest that constitutive lymphokine gene expression may be involved in the in vivo priming of LGL.
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PMID:Differential regulation of interleukin-1 gene expression in human CD3- large granular lymphocytes. 214 33

The role of previously defined thymocyte (Thm) growth factors in interleukin (IL)-7-induced Thm growth has not been fully elucidated. Therefore, experiments were designed to examine the capacity of IL-7 to: (i) directly induce Thm proliferation in the absence of experimental and known physiologic costimulators of Thm mitogenesis, and (ii) synergize with other Thm growth factors in supporting Thm proliferation. The data indicate that IL-7 is directly mitogenic for Thm; that is, IL-7 induces Thm proliferation in the absence of experimental comitogens such as concanavalin A, phytohemagglutinin, and phorbol myristate acetate and in the presence of neutralizing antibodies to murine IL-1 alpha, IL-1 beta, IL-2, IL-2 receptor (IL-2R)(p55), IL-2R(p70), IL-4, IL-6, and tumor necrosis factor (TNF). We also tested previously described Thm growth factors, i.e., IL-2, IL-4, IL-6, and TNF-alpha, for the capacity to synergize with IL-7 in Thm growth. Our results indicate that IL-2, IL-6, and TNF-alpha, but not IL-4, synergize with IL-7 in supporting Thm proliferation. These data suggest that IL-7 functions alone and in a synergistic fashion with other cytokines to regulate Thm growth.
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PMID:Synergism of interleukin 7 with the thymocyte growth factors interleukin 2, interleukin 6, and tumor necrosis factor alpha in the induction of thymocyte proliferation. 218 44


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