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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kaposi's sarcoma (KS) is the most frequent neoplastic complication observed in HIV-infected patients. Cutaneous KS is the most common manifestation but visceral and lymph node involvement may occur. HIV-infection does not only lead to a decrease of certain cell types (CD4 T-lymphocytes), but also modifies the function of non-infected cells such as B-lymphocytes and NK-cells by upregulating cytokine release of IL-1, IL-6, GM-CSF, IFN-gamma and TNF-alpha. These multifunctional mediators show both autocrine and paracrine proliferative effects on normal endothelial cells and AIDS-related KS-cells. Using ELISA-, RIA- and IRMA-techniques we analysed the influence of seven cytokines (IL-1beta, IL-6, TNF-alpha, GM-CSF, IFN-alpha, IFN-beta, IFN-gamma) and the soluble IL-2 receptor (sIL-2R) on the growth of eight different KS-derived cell lines compared with eight fibroblast cell lines, established from skin biopsies of HIV-positive individuals. Furthermore, we analysed the dose-dependent effect of the above mentioned cytokines on KS-derived cells in vitro. The KS-derived cell culture medium demonstrated significantly higher concentrations than the fibroblast cell lines in view of the following cytokines: sIL-2R, IL-1beta, IL-6, TNF-alpha, GM-CSF, IFN-gamma (p<0.05). The most pronounced differences between KS-cells and fibroblasts were observed for IL-1beta and IFN-gamma. The antiproliferative effect of IFN-beta and IFN-gamma began at a concentration of 20 and 50 IU/ml, respectively, whereas for IFN-alpha an antiproliferative effect was observed at a concentration of 100 U/ml. Furthermore we observed a proliferative effect in low concentrations (2-5 IU/ml) of IFN-gamma in our in vitro model
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PMID:Cytokine profile of HIV-positive Kaposi's sarcoma derived cells in vitro. 1008 75

We performed a placebo-controlled study to evaluate the effects of immunomodulatory treatment with thalidomide on HIV levels, TNF-alpha levels, and immune status of 31 HIV-infected individuals, after temporary suppression of viral replication with antiretroviral drugs. Treatment with a combination of zidovudine and lamivudine (ZDV/LMV) for 14 days resulted in a median decline in plasma viremia of 1.94 log10 RNA equivalents/ml. After discontinuation of ZDV/LMV, thalidomide therapy (200 mg/day for 4 weeks) did not retard the prompt return of HIV titers to the pretreatment levels, and had no effect on plasma levels of TNF-alpha. In contrast, thalidomide treatment resulted in significant immune stimulation. We observed increased levels of plasma soluble IL-2 receptor, soluble CD8 antigen, and IL-12 (p < 0.01 for all parameters), as well as increased cutaneous delayed-type hypersensitivity reactions to recall antigens (p < 0.01) in thalidomide-treated patients. These changes were associated with a median increase in HIV titer of 0.2 log10 RNA equivalents/ml in the thalidomide-treated group (p < 0.05), which resolved after stopping the drug. Further studies were performed in vitro to elucidate the mechanism of thalidomide-induced immune stimulation. When purified T cells from HIV-infected individuals were stimulated by immobilized anti-CD3 in the presence of thalidomide, a costimulatory effect of the drug was observed, resulting in increased production of IL-2 and IFN-gamma, and increased T cell-proliferative responses. Further experiments showed that thalidomide increased IL-12 production by antigen-presenting cells in a T cell-dependent manner. Our findings suggest a potential application for thalidomide as a novel immune adjuvant in HIV disease.
AIDS Res Hum Retroviruses 1999 Sep 01
PMID:Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients. 1048 Jun 30

The authors have previously reported that the soluble serum form of the alpha subunit of the IL-2 receptor (sIL-2Ralpha), whose natural half-life is approximately 40 min, survived much longer in the circulation when bound by a specific antibody. In the present study, the authors evaluated the extent to which sIL-2Ralpha protected IL-2 in freshly collected serum using biochemical analyses, and a functional CTLL-2 assay. In particular, sIL-2Ralpha protected IL-2 from forming complexes with alpha(2)-macroglobulin and from inactivation in vitro. In addition, the authors demonstrated that the anti-IL-2Ralpha monoclonal antibody 7G7/B6, which does not inhibit the binding of IL-2 to its binding site on sIL-2Ralpha, protected IL-2 from degradation and inactivation in vivo in the presence of sIL-2Ralpha. Both(125)I-labelled and unlabelled IL-2 were injected into mice preinjected with humanized anti-Tac (hTac) or 7G7/B6 and sIL-2Ralpha, or sIL-2Ralpha alone. Using size-exclusion HPLC, ELISA, and CTLL-2 cell proliferation assays, we observed that the presence of 7G7/B6 led to formation of complexes with sIL-2Ralpha and increased the serum levels of IL-2 more than 3- to 40-fold those of groups receiving IL-2 alone, sIL-2Ralpha, or hTac. Taken as a whole, these results suggest that the complex of 7G7/B6 and sIL-2Ralpha not only prolongs the survival of IL-2 in vivo, but also maintains the bioactivity of IL-2. The use of antibodies against endogenous soluble receptors could increase the in vivo survival of cytokines, protect their bioactivity and thereby facilitate their clinical use in the treatment of various malignancies and AIDS.
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PMID:Use of an antibody against the soluble interleukin 2 receptor alpha subunit can modulate the stability and biodistribution of interleukin-2. 1062 32

This work shows the presence of structural and physical analogies between some precise sites of the trimeric ectodomain of the transmembrane envelope glycoproteins of the HIV, SIV and FIV viruses and some precise sites of the interleukin 2 of the corresponding infected species (man, monkey, cat, respectively). In all the cases examined, the ectodomains of GP41 (HIV-SIV) and GP36 (FIV), because of their trimeric structure, place in the same spatial configuration the same amino acids clusters as the IL-2 amino acids clusters interacting with two, or even three, of the alpha, beta and gamma subunits of the IL-2 receptor. The molecular mimicry identified between the viral transmembrane glycoprotein and IL-2 is probably most useful for the virus and seems to be specific of each species; it is presumably due to a strategy common to the retroviruses associated with AIDS (HIV, SIV, FIV).
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PMID:Molecular mimicry between the trimeric ectodomain of the transmembrane protein of immunosuppressive lentiviruses (HIV-SIV-FIV) and interleukin 2. 1114 25

The thiol antioxidant N-acetyl- L-cysteine (NAC), known as a precursor of glutathione (GSH), is used in AIDS treatment trials, as a chemoprotectant in cancer chemotherapy and in treatment of chronic bronchitis. In vitro, GSH and NAC are known to enhance T cell proliferation, production of IL-2 and up-regulation of the IL-2 receptor. The 120-kD CD30 surface antigen belongs to the tumour necrosis factor (TNF) receptor superfamily. It is expressed by activated T helper (Th) cells and its expression is sustained in Th2 cells. We have analysed the effect of GSH and NAC on the cytokine profile and CD30 expression on human allergen-specific T cell clones (TCC). TCC were stimulated with anti-CD3 antibodies in the presence of different concentrations of GSH and NAC. Both thiols caused a dose dependent down-regulation of IL-4, IL-5 and IFN-gamma levels in Th0 and Th2 clones, with the most pronounced decrease of IL-4. Furthermore, they down-regulated the surface expression of CD30, and the levels of soluble CD30 (sCD30) in the culture supernatants were decreased. In contrast, the surface expression of CD28 or CD40 ligand (CD40L) was not significantly changed after treatment with 20 m M NAC. These results indicate that GSH and NAC favour a Th1 response by a preferential down-regulation of IL-4. In addition, the expression of CD30 was down regulated by GSH and NAC, suggesting that CD30 expression is dependent on IL-4, or modified by NAC. In the likely event that CD30 and its soluble counterpart prove to contribute to the pathogenesis in Th2 related diseases such as allergy, NAC may be considered as a future therapeutic agent in the treatment of these diseases.
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PMID:Thiols decrease cytokine levels and down-regulate the expression of CD30 on human allergen-specific T helper (Th) 0 and Th2 cells. 1129 19

Human immunodeficiency virus (HIV), the retrovirus associated with acquired immune deficiency syndrome (AIDS), induces a spectrum of immune abnormalities including a state of anergy in the host. This state is due to the binding of HIV envelope glycoprotein moieties to CD4 molecules and chemokine receptors. Resulting decrease in antigen presenting cell function and the interference with functioning of positive and negative regulatory molecules involved in signal transduction have an anergizing effect on the immune system. This effect is exemplified by diminished production of interleukin-2 (IL-2) and interferon-gamma and reduced expression of IL-2 receptor by CD4 helper cells of HIV patients. These immune abnormalities lead to clinically relevant immunological phenomena such as Type-1 to Type-2 switch, decrease in delayed-type hypersensitivity dermal reaction, etc. Insight into these interesting phenomena could pave the path for favorably altering the immunological milieu for drug and vaccine trials.
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PMID:Anergy and human immunodeficiency virus infection. 1135 64

Immune cells secrete a variety of cytokines that have a profoundly significant influence on the immune system. For example, cytokines secreted by T-helper cells have a role in cellular immune response (Th1 cytokines) and in antibody production (Th2 cytokines). Interleukin 2 (IL-2) is used therapeutically for immune modulation, most specifically in cancer therapy. The following report describes the mechanisms of IL-2/IL-2 receptor interaction and summarizes the rationale for using IL-2 in HIV-infected patients and briefly describes recent and ongoing clinical trails using IL-2 in HIV/AIDS disease (intravenous IL-2 therapy and subcutaneous IL-2 therapy). In one study of patients with moderate stage HIV disease, subjects taking a maximum tolerated dose of IL-2 at 12 to 15 MIU/day demonstrated durable increases in CD4 counts and a near normal return in value. Relative to the published reports, low circulating CD4 counts and high HIV viral burden appeared to be independent determinants of a poor response to IL-2. However, aggressive combination therapy with IL-2 and highly active anti-retroviral therapy (HAART)(e.g., ACTG 328) holds promise for an improved immune restorative response even in patients with advanced disease.
AIDS Patient Care STDS 1998 Mar
PMID:Interleukin-2 therapy in HIV infection. 1136 33

In an interview, Kendall A. Smith, M.D., whose laboratory identified the IL-2 molecule and the IL-2 receptor, discusses a current study on administering low, daily doses of IL-2 to HIV patients who are also on HAART. One purpose of the study is to see if IL-2 increases the recovery of CD4 cells over an extended period. The second purpose is to see if a patient's immune system might be able to control the virus when HAART is interrupted, but IL-2 treatment is continued. The study results are described. Dr. Smith also discusses the history of IL-2 and other trials currently studying IL-2.
AIDS Treat News 1999 Oct 15
PMID:IL-2 low dose and treatment interruption: interview with Kendall A. Smith. Interview by John S. James. 1136 19

IL-16 is a multi-functional cytokine that uses CD4 as a receptor to signal diverse biological activities by target cells including T-lymphocytes, monocytes and eosinophils. IL-16 has been shown to repress HIV-1 infection in lymphocytes and monocytic cells and it is active against both laboratory and naturally acquired virus isolates. In lymphocytes, the repressive effect of IL-16 occurs at the level of virus transcription, while it appears to inhibit viral entry in monocytic cells. Clinical studies comparing serum IL-16 levels with the state of HIV-1 disease suggest that this cytokine is a functionally significant endogenous antiviral factor. The antiviral activity of IL-16 may be of therapeutic benefit in HIV/AIDS but its greatest potential is for immune reconstitution. Stimulation of CD4+ T-cells with IL-16 primes cells to respond to IL-2, by upregulating the expression of IL-2 receptor p75 (CD25). Co-treatment of peripheral blood mononuclear cells (PBMC) with IL-16 plus IL-2 (or IL-15) in vitro selectively expands the population of CD4+ T-cells. Clinical trials of recombinant IL-2 have already shown promise in HIV/AIDS. In combination with IL-16, the beneficial effects of IL-2 may be augmented and specifically targeted to CD4+ T-cells. Thus, IL-16 shows considerable promise as an agent for the biological therapy of HIV/AIDS.
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PMID:Prospects for IL-16 in the treatment of AIDS. 1172 16

Interleukin-2 (IL-2) belongs to a class of soluble, regulatory proteins known as cytokines. It is a 133 amino acid glycoprotein secreted by T(H) lymphocytes and other cells following activation by antigens, mitogens and other cytokines. It stimulates the proliferation and cytotoxicity of T lymphocytes. It also enhances the microbicidal and cytotoxic activities of NK cells, B lymphocytes, macrophages and monocytes. IL-2 can now be produced in unlimited quantities by recombinant DNA technology and used therapeutically to modulate the immune system in a number of diseases. A number of different studies have demonstrated its therapeutic value in HIV +ve and AIDS patients. It has been approved by US-FDA for treatment of metastatic renal cell carcinoma (RCC) and metastatic melanoma. Routine detection of soluble IL-2 receptor in blood could be useful as a diagnostic marker in some autoimmune diseases. Agents that antagonize IL-2 find application as immunosuppressants. The main adverse effect of IL-2 is capillary leak syndrome caused by increased capillary permeability and extravasation of fluid. In days to come, IL-2 is likely to play an increasingly important role in management of viral infections, malignancies and a number of other diseases conditions.
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PMID:Interleukin-2 as a therapeutic agent. 1183 57


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