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)

Stimulation of T-lymphocytes derived from some patients with common variable immunodeficiency (CVID) syndrome results in defective proliferation. The underlying mechanism is related to the inability of stimulated cells to secrete IL-2 while the expression of IL-2 receptor (IL-2R) is normal. We have identified a patient whose peripheral T-cells failed to proliferate and secrete IL-2 upon stimulation. The addition of recombinant IL-2 restored proliferation. The defect did not seem to be caused by accessory cell failure since the patient's adherent cells produced IL-1 and IL-6, and addition of allogeneic irradiated cells did not induce proliferation. Stimulation of CVID T-cells with phorbol esters and Ca2+ ionophore induced both IL-2 secretion and proliferation, indicating the absence of a defect in the transcription and/or translation of the IL-2 gene. The patient's T-cells expressed high levels of CD3. The majority of T-cells expressed the CD38 molecule which is normally found on thymocytes or activated T-cells but not peripheral blood T-cells and HLA-DR, another activation marker. However, CD25 (the IL-2R) and CD1, a marker of more immature thymocytes, were not expressed. Finally, the patient's cells were sensitive to an in vitro corticosteroid treatment. The possibilities that this patient's T-cells represent anergic T-cells or not fully matured thymocytes are discussed.
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PMID:An unusual T-cell surface phenotype in vivo correlates with the failure to proliferate and produce IL-2 in vitro in a patient with common variable immunodeficiency. 128 May 40

Dithiocarbamates and iron chelators were recently considered for the treatment of AIDS and neurodegenerative diseases. In this study, we show that dithiocarbamates and metal chelators can potently block the activation of nuclear factor kappa B (NF-kappa B), a transcription factor involved in human immunodeficiency virus type 1 (HIV-1) expression, signaling, and immediate early gene activation during inflammatory processes. Using cell cultures, the pyrrolidine derivative of dithiocarbamate (PDTC) was investigated in detail. Micromolar amounts of PDTC reversibly suppressed the release of the inhibitory subunit I kappa B from the latent cytoplasmic form of NF-kappa B in cells treated with phorbol ester, interleukin 1, and tumor necrosis factor alpha. Other DNA binding activities and the induction of AP-1 by phorbol ester were not affected. The antioxidant PDTC also blocked the activation of NF-kappa B by bacterial lipopolysaccharide (LPS), suggesting a role of oxygen radicals in the intracellular signaling of LPS. This idea was supported by demonstrating that treatment of pre-B and B cells with LPS induced the production of O2- and H2O2. PDTC prevented specifically the kappa B-dependent transactivation of reporter genes under the control of the HIV-1 long terminal repeat and simian virus 40 enhancer. The results from this study lend further support to the idea that oxygen radicals play an important role in the activation of NF-kappa B and HIV-1.
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PMID:Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. 131 83

Cytokines play a crucial role in the inflammatory and immune responses. The activity of cytokines is counterbalanced by specific inhibitors with some functioning as receptor antagonists. Inhibitors to interleukin 1 and tumor necrosis factor may have therapeutic potential in conditions such as inflammatory arthritis, diabetes mellitus, disseminated intravascular coagulopathy and septic shock. The ability to modulate host defenses with cytokines and cytokine antagonists may also have applications in the fields of transplantation, oncohematology and immunodeficiency.
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PMID:Immunomodulating functions of tumor necrosis factor and interleukin 1 inhibitors. 131 88

The acquired immunodeficiency syndrome (AIDS) is a severe disease. Lung, brain and digestive complaints that result in opportunistic infections and neoplasms are the most documented. The endocrine disorders, the description of which is recent on the basis of post-mortem data, motivated some authors to undertake studies in order to evaluate endocrine function in patients infected with human immunodeficiency virus (HIV). An increase in serum cortisol level due to stress adaptation in the early stage of the disease is reported, whereas peripheral adrenal insufficiency, although unusual, appears in the late stage. Hypogonadism is common in men with HIV infection but its origin is discussed, central or peripheral. The thyroid function is generally preserved, but low T3 syndrome which correlates with bad prognosis may be observed. Anterior hypopituitarism, which is rare, hyponatremia more frequent because of its etiopathogenic factors in AIDS, constant and precocious hyperprolactinemia, are noticed. The episodes of asymptomatic or severe hypoglycemia may be explained by inanition and side effects of drugs. The non-specificity of the clinical manifestations of endocrine dysfunction masked by the classic signs of AIDS, shouldn't make forget the systematic search of glandular abnormalities as soon as an evocative symptomatology is conspicuous. The mechanisms of endocrine complications are badly known, but opportunistic infections, drugs, particularities related to the structure of HIV and interleukin 1 (IL1) surely play a role. The recognition of endocrine disorders is essential for optimal therapy because, unknown, their evolution is dramatic.
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PMID:[Endocrinological aspects of acquired immunodeficiency syndrome (AIDS)]. 140 12

The effects of human interferon-alpha (IFN-alpha) or maltose-stabilized IFN-alpha (MS-IFN-alpha) on IL-2 production by PHA- or anti-CD3 mAb-stimulated MOLT 16 cells, a human leukemic T cell line, were studied. MS-IFN-alpha is an IFN-alpha-containing powder in which maltose was used as an excipient, and has been shown to have a positive effect on human immunodeficiency virus (HIV)-infected patients. In this study, MS-IFN-alpha powder was dissolved in a culture medium and used for the experiments. IL-2 production by PHA- or anti-CD3 mAb-stimulated MOLT 16 cells was augmented by coculturing with IFN-alpha or MS-IFN-alpha. The augmentation of IL-2 production by IFN-alpha or MS-IFN-alpha was completely abrogated by rabbit anti-IFN-alpha antibody. We have previously shown that IL-2 production by PHA-stimulated MOLT 16 cells is augmented by coculturing with IL-1. Furthermore, IL-2 production by PHA-stimulated MOLT 16 cells was also augmented by human TNF-alpha in a dose-dependent manner. The TNF-alpha-induced augmentation was completely abrogated by rabbit anti-TNF-alpha antibody. Interestingly, both IFN-alpha and MS-IFN-alpha synergized with rIL-1 alpha or TNF-alpha resulting in IL-2 production being augmented far more effectively than either cytokine alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The immunomodulatory role of IFN-alpha or maltose-stabilized IFN-alpha on T-cell activation. 142 Jun

Human interleukin 1 receptor antagonist protein (IRAP) is a specific antagonist of interleukin 1 (IL-1) action in both in vitro and in vivo experimental models. Presently, the significance of this protein in human pathophysiology is unknown. In the present study, monoclonal antibodies against IRAP were prepared and used to demonstrate IRAP expression in human tissues, immunohistochemically. Specifically, this study focused on lymphoid tissues and granulomatous inflammatory reactions since IL-1 is believed to play roles in lymphocyte development and inflammation. In addition, these tissues were also stained for IL-1 beta to compare the expression of agonist and antagonist. These findings indicate that IRAP expression is largely limited to macrophages and their derivatives. Strong IRAP expression was observed in germinal center macrophages of lymph nodes, spleen, and tonsil. In contrast, IL-1 was marginally expressed in these organs. Granulomas associated with active M. tuberculosis infection, sarcoidosis and foreign bodies all contained strongly IRAP positive cells, which included macrophages, epithelioid cells and multinucleate giant cells. Unlike reactive lymphoid tissue, tuberculous and sarcoid granulomas also contained IL-1 positive cells which included macrophages and their derivatives, as well as some stromal cells. Foreign body lesions showed minimal IL-1 expression. Interestingly, granulomas in patients with acquired immunodeficiency disease (AIDS) associated with M. avium-intracellulare contained IRAP positive cells but were negative for IL-1 expression. Taken together, these findings suggest that IRAP takes part in both physiologic and pathologic reactions. Moreover, they provide a basis to design future studies to determine the precise contribution of IRAP to these reactions.
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PMID:Immunohistochemical demonstration of interleukin-1 receptor antagonist protein and interleukin-1 in human lymphoid tissue and granulomas. 153 98

The ability of the human immunodeficiency virus (HIV) to replicate in CD+ T lymphocytes and mononuclear phagocytes(MP) is strongly influenced by immunoregulatory cytokines. In the T cell system, interleukin-2 (IL-2) provides a mitogenic signal leading to both cell proliferation and virus replication. Among other HIV-inductive cytokines, only tumor necrosis factor-alpha or -beta (TNF-alpha/-beta) have been shown thus far to trigger virus expression both in T cells and MP. The mechanism of action of TNF involves the activation of the cellular transcription factor NF-kB which binds to specific consensus sequences present in the enhancer region of the HIV proviral LTR. In addition, several other cytokines (including colony stimulating factors, IL-1, IL-3, and IL-6) have demonstrated upregulatory effects on HIV production in MP, whereas nonimmune interferons (INF-alpha/-beta) have been shown to suppress HIV replication in T cells and MP by acting at different phases in the virus life cycle. Finally, cytokines such as TGF-beta, IFN-gamma, and IL-4 have demonstrated either upregulatory or suppressive effects on virus expression depending on the experimental conditions. This scenario indicates that HIV expression is under the control of a complex network of immunoregulatory cytokines, in addition to its own endogenous regulatory proteins, suggesting that new pharmacologic strategies may be aimed at either mimicking or interrupting cytokine-dependent virus expression. In this regard, a number of different physiologic and pharmacologic agents capable of interfering with cytokine-mediated events, including glucocorticoids, anti-oxidants, such as N-Acetyl-L-Cysteine (NAC), and retinoic acid (RA) have already been shown to profoundly affect HIV replication in vitro.
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PMID:The effect of cytokines and pharmacologic agents on chronic HIV infection. 154 Apr 7

Disseminated Mycobacterium avium infections are common in patients with AIDS and result in a reduced life expectancy. Human monocytes/macrophages are important target cells for both human immunodeficiency virus (HIV) and M. avium. We have studied the interaction in vitro of M. avium and HIV type 1 (HIV-1) in human macrophages. Human monocytes isolated from the peripheral blood of healthy individuals were infected with HIV-1, M. avium, or both. The intracellular growth of M. avium and the replication of HIV-1 were monitored for up to 5 weeks. Intracellular mycobacterial growth was seen in all M. avium infected cell cultures and was paralleled by increased production of interleukin 1 alpha and beta. Preinfection of the macrophages with HIV-1 reduced the interleukin 1 production and accelerated the intracellular growth of M. avium. These findings may explain in part the impaired control of mycobacterial infections seen with patients with AIDS.
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PMID:Human immunodeficiency virus type 1 enhances intracellular growth of Mycobacterium avium in human macrophages. 158 13

Intracerebroventricular (i.c.v.) infusion of glycosylated recombinant gp120, the envelope protein of human immunodeficiency virus, in various doses (100 ng to 4 micrograms) resulted in detection of interleukin 1 (IL-1) activity in a high percentage (61%; 33 of 54) of rat brains, whereas IL-1 was very rarely detected in brains of animals infused with several control substances (4%; 1 of 28). To detect IL-1, clarified glial lysate of diencephalon plus brainstem was subjected to gel exclusion chromatography and fractions were assessed for thymocyte stimulation. IL-1 was seen 2, 6, and 24 hr postinfusion. i.c.v. gp120 also produced known effects of IL-1 in brain, elevating steroid concentration in plasma and decreasing cellular immune responses [natural killer (NK) cell activity and mitogenic response to Con A] of blood and splenic lymphocytes. When gp120 was infused together with alpha-melanocyte-stimulating hormone (20 ng), which blocks many biological actions of IL-1, gp120 no longer elevated steroids or decreased NK cell activity. After intravenous gp120, IL-1 was not found in brain or plasma, indicating that stimulation of IL-1 in brain by i.c.v. gp120 was not due to gp120 affecting infiltrating cells from blood or to elevated circulating IL-1. That induction of IL-1 in brain might have resulted from lipopolysaccharide (LPS) in the gp120 solution was ruled out by studies showing that (i) heating of the infusion solution, which does not affect the capacity of LPS to induce IL-1, eliminated the ability of gp120 infusion to induce brain IL-1, and (ii) gp120 induced IL-1 in brains of LPS-resistant C3H/HeJ mice. Injection of gp120 directly into the hippocampus stimulated IL-1 more readily than i.c.v. infusion. Thymocyte stimulation produced by active fractions of gp120-infused brains was blocked by monoclonal antibody to IL-1 receptors. These findings indicate that elevation of IL-1 in brain can result from infection with human immunodeficiency virus and may be responsible for certain abnormalities (e.g., elevated activity of pituitary-adrenal axis) seen in AIDS patients.
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PMID:Human immunodeficiency virus glycoprotein (gp120) infused into rat brain induces interleukin 1 to elevate pituitary-adrenal activity and decrease peripheral cellular immune responses. 166 89

Induction of lymphokine-activated killer (LAK) activity by IL-2 has been described and characterized as broadly cytolytic activity against both fresh and cultured tumors. rIL-7 in the absence of IL-2 also induces LAK activity in human cells. This activity is unique for IL-7, because it is not shared by other cytokines including IL-1, IL-4, IL-6, and TNF-alpha. IL-7 also induces either de novo or increased expression of the surface markers CD25 (Tac, IL-2R alpha-chain), CD54 (ICAM-1), Mic beta 1 (IL-2R beta-chain) and CD69 (early T cell activation Ag). IL-7-induced LAK activity is independent of IL-2 secretion, because it is not abrogated by IL-2 antisera. The LAK precursor responding to IL-7 stimulation is enriched in the null cell fraction as has been demonstrated for IL-2-induced LAK cells. TGF-beta and IL-4 interfere with generation of LAK activity by IL-7. Anti-IL-4 antiserum enhances IL-7-induced LAK activity and augments induction of surface marker expression by IL-7. This may be indirect evidence that IL-7 stimulation leads to induction of IL-4 activity. Our results describe the activation of mature lymphoid cells by IL-7. This and the previously described role of IL-7 in lymphohemopoiesis makes it a cytokine of potential therapeutic value for treatment of immunodeficiency states and possibly the immunotherapy of cancer.
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PMID:IL-7 induces human lymphokine-activated killer cell activity and is regulated by IL-4. 167 Jun 2


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