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)

We have examined the effect and potential mechanism of Cyclosporin A (CsA) on the Interleukin-2-receptor alpha chain (IL-2R alpha) expression in human T-lymphocytes. CsA pretreatment of PHA-activated T-cells led to 30-50% decrease in Tac antigen surface expression and a concomitant decrease in the steady state IL-2R alpha mRNA levels. Transacting factors which recognize a kB-like sequence present in the IL-2R alpha chain regulatory region have been suggested to participate in the transcriptional regulation of the IL-2R alpha gene. Using oligonucleotides corresponding to the 5' regulatory region of the IL-2R alpha gene (i.e. 245 to 291 bp upstream of the start codon) and nuclear extract from resting T lymphocytes, we detected two specific bands by gel mobility shift assay. One of these bands is specifically increased after stimulation with phytohemagglutinin (PHA) and it is inhibited by CsA pretreatment. The same pattern of binding activity has been observed with the tandem repeat of NF-kB binding site present in the enhancer element of the human immunodeficiency virus long terminal repeat (HIV-1 LTR). These data suggest that CsA affects IL-2R receptor alpha chain expression by inhibiting the interaction of transacting factors to kB-like sequences after PHA activation. These findings may be of some relevance for the understanding of the immunosuppressive effects of CsA in normal human T lymphocytes.
Eur Cytokine Netw
PMID:Cyclosporin A inhibits induction of IL-2 receptor alpha chain expression by affecting activation of NF-kB-like factor(s) in cultured human T lymphocytes. 212 97

Dehydration-rehydration liposome vesicles (DRVs) containing various cytokines were evaluated for their ability to induce delayed-type hypersensitivity (DTH) and humoral immunity to the recombinant envelope protein rgp120 of the MN strain of human immunodeficiency virus type 1 (HIV-1). The DRVs trapped approximately 25% of the radiolabeled cytokines and approximately 17% of the radiolabeled rgp120 that were added. The level of trapping was greater than the aqueous volume of the DRVs, indicating association of the proteins with the lipid bilayer. Flow cytometric analysis using antibody to rgp120 or the V3 loop of rgp120 showed the diameter of the DRVs to be 2-7.5 microns. Transmission electron microscopy confirmed the heterogeneity in size of the DRVs and revealed morphological heterogeneity. Transmission electron microscopy with immunogold labeling also revealed the presence of rgp120 on the surface of the DRVs. In vitro bioassays demonstrated slow leakage of biologically active cytokines from DRVs soaked in tissue culture medium containing serum. Mice injected subcutaneously three times at 14-day intervals with DRVs containing 15 micrograms of rgp120 plus interleukin 6 (IL-6) or interferon gamma (IFN-gamma) produced significantly greater DTH responses than mice injected with DRVs containing rgp120 alone. Soluble rgp120 plus soluble IFN-gamma produced DTH in some experiments, but of lower magnitude than the comparable DRVs. Interleukin 6, but not IFN-gamma, increased the antibody titer to rgp120 when included in the DRVs. The mice did not develop antibodies to IFN-gamma or IL-6. Induction of DTH by vaccines may increase protection from viral pathogens such as HIV. Cytokine-containing liposomes may be an effective adjuvant for the induction of a DTH response to envelope-antigen subunit vaccines.
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PMID:Cytokine-containing liposomes as adjuvants for HIV subunit vaccines. 749 39

Children or adults with the primary immunodeficiency disease, common variable immunodeficiency (CVI), have abnormally low levels of at least two of the three serum Ig isotypes. Although there appear to be intrinsic B cell defects, many have poor T cell proliferation and deficient secretion of IL-2, IL-4, IL-5 interferon-gamma, and B cell differentiation factor. Because the addition of various T cell factors can enhance Ig secretion in vitro in CVI, we have hypothesized that the B cells in this disease may be defective because they lack appropriate investigating the in vivo effects of recombinant IL-2 using a new biologic, polyethylene glycol-conjugated recombinant IL-2 (PEG-IL-2). In these studies, CVI patients were treated with weekly subcutaneous injections of PEG-IL-2. After 12 weeks, each patient had enhanced T cell proliferation, normal IL-2 production, boosted BCDF secretion, and B cells responsive to differentiation signals. During PEG-IL-2 treatment, four of five patients produced detectable serum antibody to keyhole limpet hemocyanin. These data suggest that CVI, which has the phenotype of B cell deficiency, may be caused by a lack of appropriate T cell signals for B cell maturation.
J Interferon Cytokine Res 1995 Mar
PMID:Immunologic effects of low-dose polyethylene glycol-conjugated recombinant human interleukin-2 in common variable immunodeficiency. 758 74

Phagocytosis of Mycobacterium tuberculosis by human monocytes or macrophages is classically followed by granuloma formation in vivo. Granuloma are comprised of cells of the monocyte lineage together, in many instances, with antigen-specific T lymphocytes. Development of granuloma depends upon recruitment of both cell types, but recruitment of monocytes is pivotal as these cells secrete anti-mycobacterial cytokines and IL-8, a T cell chemoattractant. We have therefore investigated gene regulation of Monocyte Chemotactic Protein 1 (MCP-1), an important monocyte chemotactic cytokine, following phagocytosis of particulate material (latex beads and zymosan) and live M. tuberculosis by two human monocytic cell lines. In THP-1 cells and phenotypically more differentiated Mono Mac 6 cells, MCP-1 mRNA accumulation was first detectable by Northern analysis of 4 hours and increased over 24 hours. Magnitude and kinetics of MCP-1 gene expression was independent of the biochemical nature of the phagocytic stimulus, M. tuberculosis strain virulence or pre-treatment with anti-TNF. In contrast to the uniform effect of different phagocytic stimuli on MCP-1 gene expression, we have shown that M. tuberculosis but not latex or zymosan, increased IL-8 gene expression, a chemotactic agent for T cells. In additional experiments with THP-1 cells infected with human immunodeficiency virus (HIV), viral infection did not alter MCP-1 gene expression following phagocytosis. MCP-1 gene expression appears to be a conserved antigen-independent response of human monocytic cells which is activated following particulate phagocytosis. MCP-1 gene expression may thus be involved in recruitment of monocytes during granuloma formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytokine 1993 Mar
PMID:Phagocytosis of Mycobacterium tuberculosis or particulate stimuli by human monocytic cells induces equivalent monocyte chemotactic protein-1 gene expression. 768 73

HIV infection is associated with abnormalities of cytokine production. A number of cytokines (IL-1, IL-6, TNF-alpha, interferons-alpha and -gamma) are produced at an increased level in vivo, whereas the production of IL-2 is decreased. This latter abnormality certainly plays an important role in the immunodeficiency of AIDS patients. Monokines (IL-1, IL-6, TNF-alpha) stimulate HIV replication in vitro, whereas the interferons decrease it. Cytokine effects on the in vivo spreading of HIV remain however to be determined. Cytokines may also be mediators of the clinical manifestations of AIDS. IL-1, IL-6 and TNF-alpha may induce tissue lesions of opportunistic infections and HIV encephalopathy. Cytokines, and mainly IL-6, may stimulate the growth of malignant cells in Kaposi sarcomas and in lymphomas. A better knowledge of the roles of cytokines in HIV infection may allow new therapeutic approaches using either recombinant cytokines or specific antagonists, with the aim of inhibiting both HIV spreading and the clinical manifestations of the infection.
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PMID:[Cytokines and AIDS]. 768 34

Cytokine production of unstimulated and mitogen-stimulated peripheral blood mononuclear cells of 31 children vertically infected with human immunodeficiency virus type 1 (HIV) and with different patterns of disease progression was evaluated to establish possible correlations between the immunologic and the clinical findings. Production of interferon gamma and interleukin-2 (type 1 cytokines), and of interleukin-4 and interleukin-10 (type 2 cytokines), was analyzed in seven symptom-free patients (Centers for Disease Control and Prevention class P-1B), 10 patients with mild symptoms (class P-2A), and 14 patients with severe symptoms (class P-2B-F). Cytokine production was compared with that of 10 age- and sex-matched control subjects who were seronegative for HIV. The HIV-infected patients produced significantly fewer type 1 cytokines and significantly more type 2 cytokines than the uninfected control subjects. No differences in the production of interferon gamma and interleukin-2 were detected among the different clinical categories of HIV-infected patients. In contrast, interleukin-4 production was augmented in the patients with class P-2A (p < 0.05) and class P-2B-F HIV infection (p < 0.03), in comparison with the children with class P-1B infection. The increase in interleukin-4 production was paralleled by an increase in the number of children with hyperimmunoglobulinemia E in each of the clinical groups (0% in class P-1B; 40% in class P-2A; and 71% in class P-2 B-F infection). Similarly, interleukin-10 production was increased both in patients with class P-2A and in those with class P-2B-F infection, in comparison with the children with class P-1B disease (p < 0.006 and < 0.04, respectively). These data indicate (1) that vertically acquired HIV infection results in decreased production of type 1 cytokines and in increased production of type 2 cytokines, and (2) that an increased production of type 2 cytokines correlates with hyperimmunoglobulinemia E and is present in, and may be characteristic of, the symptomatic phases of childhood HIV infection.
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PMID:Immunologic characterization of children vertically infected with human immunodeficiency virus, with slow or rapid disease progression. 786 94

Serum immunoreactive interleukin (IL-)1 alpha, IL-4, IL-6 and tumor necrosis factor (TNF) alpha were measured in 42 patients with primary hypogammaglobulinemia (25 common variable immunodeficiency (CVI), 10 congenital hypogammaglobulinemia (CH), 7 X-linked agammaglobulinemia (XLA), and in 21 healthy controls. The cytokine levels were correlated to other immunological parameters including serum levels of neopterin and soluble CD8 (sCD8) antigen. IL-6 was detectable in 48% and IL-4 in 36% of the CVI patients, but in none of the controls. Seventy-five percent of the CVI patients with elevated IL-4 levels had detectable IL-6. In contrast, no patients in the XLA group and only three CH patients had detectable IL-4 or IL-6 levels. TNF alpha and IL-1 alpha were detected in only a few serum samples with no significant differences between patients and controls. In the CVI group elevated IL-6 levels were significantly associated to reduced numbers of CD4+ and CD19+ lymphocytes, elevated levels of neopterin and sCD8 antigen, and occurrence of splenomegaly and bronchiectasis. The raised IL-6 levels were confirmed in longitudinal testing, probably reflecting a characteristic immunological dysregulation in these patients. Cytokine alterations may play a role in the pathogenesis of the immunodeficiency and for the clinical manifestations in CVI patients. Alternatively, elevated cytokine levels may be only a marker of chronic immune activation, particularly in monocytes, possibly delineating a distinct subgroup of patients within the heterogeneous CVI group.
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PMID:Elevated serum levels of interleukin-4 and interleukin-6 in patients with common variable immunodeficiency (CVI) are associated with chronic immune activation and low numbers of CD4+ lymphocytes. 790 14

Cytokine dysregulation in human immunodeficiency virus type 1 (HIV-1) infection has been documented in numerous studies and has been cited as an important component in the pathogenesis of this retroviral infection. Pharmacological modification of cytokine dysregulation, therefore, has been suggested as a therapeutic modality for HIV-1 infection. Dr. Dezube of Beth Israel Hospital (Boston) concisely reviews the state of our knowledge regarding the effects of pentoxifylline on expression of tumor necrosis factor-alpha, a cytokine known to influence HIV-1 replication and to play a possible role in the clinical manifestations of advanced infection with this virus. Pentoxifylline, a trisubstituted xanthine derivative, has been used to decrease blood viscosity and is reasonably well tolerated by most recipients of the drug. Results of preliminary studies, many of which were conducted by Dr. Dezube, suggest that use of this agent in combination with antiretroviral compounds may prove useful in the treatment of patients with HIV-1 infection.
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PMID:Pentoxifylline for the treatment of infection with human immunodeficiency virus. 791 14

A murine acquired immunodeficiency syndrome (MAIDS) is induced in genetically susceptible strains of mice inoculated with LP-BM5 murine leukemia virus. It is characterized by progressive lymphoproliferation, profound immunodeficiency, and the subsequent loss of resistance to opportunistic pathogens, including intestinal pathogens. Cellular and/or humoral immunity of gut-associated lymphoid tissues may play a key role in the elimination of these pathogens. We have previously demonstrated reductions in the number of mucosal T and B cells in MAIDS. In this study, the cytokine production by mesenteric lymph nodes (MLN) cells and their proliferative response to mitogens during MAIDS were investigated. Alterations were observed in the kinetics of MLN cell proliferation and cytokine secretion by in vitro mitogen-stimulated MLN cells during the retrovirus infection. Cytokine production was abnormally changed, with a gradual decrease in interleukin-2 (IL-2) production as well as an increase in IL-5 and IL-6 secretion. Interferon-gamma production was increased during the progression to MAIDS. The dysregulated release of cytokines by MLN cells due to retrovirus infection could lead to immune dysfunction. These data indicate that dysregulated cytokine secretion by MLN cells may be responsible for impaired mucosal immunity in AIDS, explaining the dramatic increase of opportunistic intestinal pathogens in individuals with AIDS.
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PMID:The kinetics of cytokine secretion and proliferation by mesenteric lymph node cells during the progression to murine AIDS, caused by LP-BM5 murine leukemia virus infection. 806 35

Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) have been implicated in the transition of nonreplicating latent human immunodeficiency virus (HIV) infection to the replicating state of productive infection. In HIV infection increased concentrations of these cytokines in serum have also been found in association with hypergammaglobulinemia. We have analyzed the ability of peripheral blood mononuclear cells (PBMC) of HIV-infected children to secrete IL-6 and TNF-alpha. In kinetic studies, optimum spontaneous IL-6 secretion by 1 x 10(6) PBMC was achieved at 24 hours. The mean spontaneous IL-6 and TNF-alpha concentrations secreted by PBMC of known HIV-infected children (age range, 8 months to 11 years) were 1686 and 131 pg/ml, respectively, compared with 56 and 45 pg/ml, respectively, in normal healthy controls. No significant correlation was observed between spontaneously secreted IL-6 and TNF-alpha in culture supernatants with CD4 or CD8 numbers; with serum IgG, IgA and IgM concentrations; or with lymphoproliferative responses to recall antigens. There was, however, an association between ability to secrete IL-6 with HIV-specific in vitro antibody production. Spontaneous IL-6 secretion decreased transiently after initiation of antiretroviral therapy, returning to original values with continued treatment. Cytokine derangement in HIV-infected children includes PBMC-derived spontaneous IL-6 and TNF-alpha secretion.
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PMID:Increased spontaneous secretion of interleukin 6 and tumor necrosis factor alpha by peripheral blood lymphocytes of human immunodeficiency virus-infected children. 807 36


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