Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of tumor necrosis factor (TNF)-alpha and TNF-beta by various human hematopoietic cell lines was quantitatively examined using a highly sensitive radioimmunoassay specific to TNF-alpha, or a cytolytic assay performed with mouse L929 cells. It was found that the HTLV-1-infected T cell lines examined produced large amounts of both TNF-alpha and TNF-beta. In particular, interleukin-2 (IL-2)-dependent cell lines produced large amounts of TNF-alpha. In contrast, human cell lines not infected with HTLV-1 essentially did not produce either of the TNFs. It was also found that the high production of TNF-alpha by HTLV-1-infected cells partially correlated to their high sensitivity to human immunodeficiency virus (HIV) infection. Treatment of MT-4 cells, one of the most HIV-sensitive HTLV-1-infected cell lines, with antibody specific to TNF-alpha reduced their sensitivity to HIV infection.
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PMID:Production of tumor necrosis factors by human T cell lines infected with HTLV-1 may cause their high susceptibility to human immunodeficiency virus infection. 235 83

Peripheral blood lymphocytes from five hypogammaglobulinemic patients suffering from common variable immunodeficiency (CVID) were stimulated with Staphylococcus aureus Cowan I (SAC) and pokeweed mitogen (PWM). The assays were substituted with interleukin-2 (IL-2) and interleukin-6 (IL-6) in different combinations. In three patients who were deficient for IgM in vivo a combination of SAC and IL-2 induced a normal IgM synthesis in vitro. In these patients a deficient IL-2 synthesis is probably the cause of CVID. In only one patient a "class switch" from IgM to IgG was detectable. Stimulation with PWM which is T-cell-dependent induced in one out of the five patients a normal IgM synthesis. Another CVID patient showed no defect in IgM or IgG synthesis in vitro. With these in vitro assays it seems possible to identify CVID patients who might profit from a therapy with human IL-2 in vivo.
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PMID:[Effects of IL-2 and IL-6 on the immunoglobulin synthesis of lymphocytes from CVID patients]. 237 34

In this study we analyzed the ability of peripheral blood mononuclear cells (PBMC) from hemophilic patients (He) with negative or positive serology for the human immunodeficiency virus (HIV), to increase natural killer (NK) cytotoxicity upon stimulation with physiological and non physiological agents. Purified interleukin-2 (IL-2), the interferon (IFN)-inducer polyinosinic polycytidylic acid (PIC), recombinant alpha- and gamma-IFN and the protein kinase activator phorbol myristate acetate (PMA) were used as stimulatory agents. The NK functional response was correlated with the presence of PBMC bearing phenotypic markers of activated cells (IL-2 receptor, IL-2R) and of different NK cell maturation stages. Our results demonstrate that NK effector cells with slight lytic activity (Leu 7+ CD16-) predominated in HIV+ He patients. On the other hand the occurrence of IL-2R positive cells was similarly high in both HIV+ and HIV- individuals and was probably more related to chronic replacement treatment with Factor VIII or Factor IX concentrates than to HIV infection. The ability to respond to physiological NK regulators such as IL-2 and IFNs, or to the IFN-inducer PIC was impaired in HIV+ He, especially in HIV+ LAS individuals, suggesting that the inability of these cells to increase NK cell activity after appropriate induction was due to an intrinsic defect. Since phosphoinositide turnover and subsequent protein kinase C activation are thought to be part of the physiological mechanism of NK cytotoxicity, we studied the effect of PMA on PBMC from each group of patients. The ability to respond to PMA was lost only in PBMC from HIV+ LAS patients, indicating that impairment of the NK lytic mechanism progresses as the disease gets worse.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV infection and natural killer cytotoxicity in hemophilic patients. 238 63

We performed follow-up studies in 11 patients with asymptomatic classic hemophilia, who on initial study 8 to 12 months previously had demonstrated abnormalities of lymphocyte phenotype and function. Although all subjects remained well, diminished lymphocyte proliferative responses, natural killer activity, and decreased ratios of OKT4 helper/OKT8 suppressor lymphocytes persisted. Moreover, the absolute number of OKT4 helper lymphocytes fell in the patients from a mean of 745 +/- 73/microliter in the first study to 585 +/- 50/microliter in the follow-up study, which was lower than the control value of 857 +/- 87 (P less than 0.02). Despite diminished natural killer activity, patients with hemophilia had at least normal numbers of natural killer cells as determined by the presence of the OKM1 antigens and Giemsa staining to identify large granular lymphocytes. Patients with hemophilia had more Leu 11a-positive cells than controls. Lymphocyte binding to tumor targets was not diminished, and removal of adherent cells did not increase patients' natural killer activity to control levels. Incubation of patients' lymphocytes with alpha-interferon, gamma-interferon, or interleukin-2 resulted in enhancement of natural killer activity but did not reach control levels. Thus the diminished natural killer activity in patients with hemophilia retained responsiveness to lymphokines and was caused either by an intrinsic or acquired defect in the natural killer cell or by modulation by a nonadherent cell. Subclinical immunodeficiency in patients with hemophilia is not transient and is associated with a diminished number of OKT4 helper cells, a finding often associated with clinical immunodeficiency.
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PMID:Impaired cell-mediated immunity in hemophilia. II. Persistence of subclinical immunodeficiency and enhancement of natural killer activity by lymphokines. 241 May 23

Three therapeutic areas of clinical immunology that have seen active development recently are immunopharmacology of immunosuppressive drugs; clinical use of the alpha-, beta-, and gamma-interferons and interleukin-2; and monoclonal antibody applications in marrow transplantation and antitumor therapy. Understanding of the immune regulatory systems and of the soluble factors that convey information between immune and related cells (for example, lymphokines and cytokines and their receptors) has improved substantially. New information about established immunosuppressive drugs and the introduction of new drugs are providing new opportunities for effective treatment of autoimmune diseases and improved effectiveness of organ transplantation. Clinical trials are evaluating the use of interleukin-2 in immunodeficiency disorders and neoplastic disease. Monoclonal antibodies, which have been successfully applied to diagnostic procedures, have been shown to be useful for therapeutic applications in marrow transplantation and antitumor treatment.
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PMID:Immune interventions in disease. 243 15

An overview of the immune system is presented, and the pathogenesis, transmission, diagnostic tests, diagnosis, immunotherapy, and vaccine development for human immunodeficiency virus (HIV) are reviewed. More than 42,000 cases of acquired immunodeficiency syndrome (AIDS) have now been reported in the United States, and an additional 250,000 cases are expected by 1991. The immunopathogenesis of HIV infection involves both cellular and humoral components of the immune system, with a characteristic depletion of helper T lymphocytes, impaired delayed hypersensitivity, and polyclonal B-cell activation. Monocytes and macrophages are also infected, and these cells provide a transport mechanism into the central nervous system. HIV is transmitted primarily by sexual, blood, and perinatal mechanisms. Enzyme-linked immunosorbent and Western blot assays are used in diagnostic tests, and diagnosis of AIDS is based on the presence of secondary infection or tumor at least moderately indicative of cellular immune deficiency in the absence of predisposing factors. Three approaches are being tested for treating HIV infection: immunomodulators, vaccines, and antiviral agents. Immunomodulators--including interferons, interleukin-2, immune reconstitution with bone-marrow transplantation and lymphocyte transfusions, transfer factor, granulocyte-macrophage colony-stimulating factor, inosine pranobex (isoprinosine), and naltrexone--are being tested with no great successes. Various approaches to vaccine development, including genetically engineered subunit proteins, synthetic peptides, and infectious recombinant viruses, are being considered. Primary immune responses do result from at least one vaccine. Future studies will evaluate combination approaches to therapy. HIV infections confront the health-care system with a serious challenge. It is too early to assess the effectiveness of the various therapeutic strategies for immune deficiencies caused by HIV.
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PMID:Current concepts in clinical therapeutics: immunologic treatment of human immunodeficiency virus infections. 244 17

Although the management of patients with human immunodeficiency virus infections has focused on the treatment of opportunistic infections, or acquired immune deficiency syndrome (AIDS)-related cancers in end stages of the disease, therapies now aim at preventing the natural progression of the underlying disease. In addition to zidovudine many investigational drugs are proposed to treat AIDS-related complex patients. Most of these therapies can be divided into two major groups: (1) The first group includes agents with antiretroviral properties: nucleoside analogues, such as 2'-3'-dideoxycytidine and ribavirin, suramin, antimoniotungstate (heteropolyanion-23), foscarnet (phosphonoformate), interferons, peptide T, castanospermine, dextran sulfate, AL721, or ampligen. (2) The second group aims to restore the defective immune system; it includes thymosin (thymopentin), interleukin-2, cyclosporine, plasmapheresis, bone marrow transplantation, inosine, sodium diethyldithiocarbamate, methionine-enkephalin and carrisyn. At present, no drug other than zidovudine has proved as monotherapy to lengthen survival of human immunodeficiency virus-infected patients.
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PMID:Antiviral drugs other than zidovudine and immunomodulating therapies in human immunodeficiency virus infection. An overview. 245 13

The possibility of optimizing the conditions for the cultivation of cells producing human immunodeficiency virus (HIV) was explored. The stimulating effect on the cell cultures of interleukin-2 and specific anti-interferon antibodies was examined. The individual use of interleukin-2 or anti-interferon antibody preparations did not result in any marked enhancement of HIV virus reproduction in the cells, whereas combining of interleukin-2 which stimulated proliferation of T-lymphocytes with poly- and monoclonal anti-interferon antibodies proved to be effective increasing the expression of virus-specific antigens in the cells 1.5-fold. It seems expedient to carry out further screening of different reagents and combinations thereof capable of significantly increasing HIV virus reproduction in cell cultures which would serve as the antigen for diagnostic systems.
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PMID:[Cultivation of cells producing the human immunodeficiency virus]. 245 90

Studies are presented here which demonstrate that antibodies reacting with human interleukin-2 (IL-2) are present in the sera of patients infected with the human immunodeficiency virus (HIV). It is likely that these antibodies are present due to a homology between the HIV envelope protein and IL-2. The homologues are six amino acids in length corresponding to the carboxy terminus of gp41, Leu-Glu-Arg-Ile-Leu-Leu (LERILL), and residues 14-19 of secreted IL-2, Leu-Glu-His-Leu-Leu-Leu (LEHLLL). Thus, we questioned whether antibodies made against this HIV envelope peptide would cross-react with IL-2. Not only do a high percentage of the HIV-infected individuals tested here have antibodies against LERILL, but these antibodies cross-react with the IL-2 sequence, LEHLLL. Additional antigenic processing of IL-2 is suggested by the finding that epitopes other than this sixmer are also recognized by antibodies in patients' sera. Thus, these studies suggest a mechanism by which infection with HIV can induce a potentially suppressive autoimmune response. Specifically, antibodies against an HIV envelope peptide cross-react with an epitope in IL-2.
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PMID:Individuals infected with HIV possess antibodies against IL-2. 246 43

Human immunodeficiency virus (HIV) was readily isolated by co-cultivation of patients' cells with phytohaemagglutinin-stimulated mononuclear cells from umbilical cord blood in 2 ml cultures in 24-well plates. Fluids from cultures of the MLA 144 cell line acted as an excellent source of interleukin-2, and promoted early replication of HIV in the primary cultures. Reverse transcriptase activity was commonly present at significant levels by 4-7 days. In contrast, recombinant IL-2 (recIL-2) did not promote early replication under these conditions. Adequate washing of the phytohaemagglutinin blasts was critical in this system, although others have reported it to be less important under other culture conditions. Cell concentrations and HIV: target cell ratios appeared not to play a major role in early outgrowth of virus. The particular sheep anti-alpha interferon tested resulted in a two-fold reduction in RT activity. Virus was readily transmitted in this simplified cheaper culture system.
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PMID:The value of MLA 144 culture fluid for the isolation of human immunodeficiency virus. 247 86


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