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)

Zidovudine (ZDV), an anti-human immunodeficiency virus (HIV) therapy, has been associated with reduction in mortality and improvement of patients with acquired immunodeficiency syndrome (AIDS). The ZDV recipients, however, experience a multitude of side effects of which bone marrow suppression is the most noteworthy, especially among patients with low CD4 cell counts. The effect of ZDV and interleukin-2 (IL-2) on phytohemagglutinin (PHA)-induced proliferative response of peripheral blood mononuclear cells (PBMs) from patients with HIV infection was investigated. ZDV 0.5 micrograms inhibited 40% of PHA-induced thymidine uptake in PBMs from healthy donors or patients with HIV, irrespective of their CD4 cell counts. However, IL-2 (10 U/ml) had differential effect on PHA-induced thymidine uptake that appeared to be dependent on absolute CD4 cell counts. While PBMs from patients with CD4 cell counts of 400/mm3 or more did not respond to IL-2 (low responders), IL-2 enhanced the PHA-induced thymidine uptake in PBMs from patients with CD4 cell counts less than 400/mm3 at an average of 60% (high responders). Moreover, IL-2 restored the ZDV-induced inhibition by almost 100% in the high responder group while it did not affect counts in the low responder group. The production of IL-2 in vitro, in response to PHA or recall antigens, was equivalently inhibited in both groups. These data suggest that ZDV and IL-2 could have an additive effect on immune parameters in certain groups of patients infected with HIV. The differential effect of IL-2 was independent of IL-2 receptor expression.
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PMID:Differential reconstitution of zidovudine-induced inhibition of mitogenic responses by interleukin-2 in peripheral blood mononuclear cells from patients with human immunodeficiency virus infection. 254 65

The in vitro effect of single or combined doses of zidovudine (AZT) and dideoxycytidine (ddC) on the production and utilization of interleukin-2 (IL-2) by normal human peripheral blood mononuclear cells (PBMC) was evaluated by measuring IL-2 concentrations in supernatants from PHA-stimulated PBMC cultures. Drugs were added at the beginning of the culture period and left throughout. Whereas AZT alone (1 and 10 microM) caused only a slight increase, ddC alone (1 and 10 microM) and combined AZT/ddC (1 + 1 and 10 + 10 microM) caused a considerable increase. IL-2 gene expression in the drug-treated PBMC did not increase. This finding suggested that the increased supernatant IL-2 accumulations might be caused by a drug-induced down-regulation of the IL-2 receptor alpha (IL-2R alpha, CD25). AZT decreased IL-2R alpha expression, but only slightly. In contrast, ddC alone and combined AZT/ddC decreased the CD25 molecules in a marked and dose-dependent manner. They also markedly reduced IL-2R alpha gene expression. These findings show that the dideoxynucleoside drugs tested left PHA-induced IL-2 gene activation unchanged but decreased IL-2R alpha gene activation, thus down-regulating IL-2R alpha cell-surface protein expression.
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PMID:Down-regulation of interleukin-2 receptor gene activation and protein expression by dideoxynucleoside analogs. 760

The levels of soluble form of E-Selectin (sEs), or endothelial-leukocyte adhesion molecule-1, were measured in 96 sera derived from 72 HIV-infected patients at different stages of the disease, 60 healthy blood donors, and 50 HIV-negative patients with infections, using a quantitative ELISA. Levels of sEs in HIV-infected individuals without AIDS, according to the 1993 classification system of the Centers for Disease Control, were higher than normal (mean +/- SEM 48 +/- 4 versus 35 +/- 3 ng/ml, p = 0.003). Patients with established AIDS, who were afebrile and had no evidence of acute concurrent infection, had even higher sEs serum levels (70 +/- 9 ng/ml, p = 0.009, compared to those without AIDS). A significant increase in clinical category disease progression was present. Individual concentrations of sEs correlated directly with levels of soluble intercellular adhesion molecule-1 (p < 0.00001) and IL-2 receptor (p = 0.001), but not with CD4+ T-cell counts. Zidovudine treatment was not associated with changes in sEs serum levels. Elevated sEs levels were also found in HIV-seronegative patients with other bacterial and protozoal infections. Since sEs is a biologically active molecule, further studies should investigate the pathogenetic significance of circulating sEs in HIV-related disease progression, and assess the prognostic value of sEs determination for these patients.
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PMID:Levels of the circulating cell adhesion molecule E-selectin and disease progression in HIV infection. 852 77