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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocytes from human immunodeficiency virus (HIV) patients have an increased heterogeneity of phenotype and function. In a study of 120 HIV patients we have demonstrated that they have normal monocyte differential counts but that with progression of the disease an increasing proportion of monocytes show phenotypic and functional evidence for activation or maturation. A proportion of the monocytes are larger, with increased expression of CD11b, HLA-DR, CD45 and CD16. Concomitantly there was increased expression of TNF-alpha, high constitutive synthesis of PGE2 and high plasma IL-6 levels. This suggested that there exists a more dynamic situation of recruitment, activation and maturation of peripheral blood monocytes driven by HIV infection which results in a broader phenotypic profile.
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PMID:Heterogeneity of peripheral blood monocyte populations in human immunodeficiency virus-1 seropositive patients. 146 4

An antiviral effect of prostaglandins (PGs) of the A series on the replication of human immunodeficiency virus (HIV) has been determined. In the T cell line C8166 under single growth cycle conditions, PGA1 reduced the number of infectious progeny 1000-fold in the absence of cytotoxicity. Thus, inhibition of HIV replication by PGA1 represents a true antiviral phenomenon. The number and size of virus-induced syncytia, and the amount of viral antigen were also drastically reduced. The effect was specific for PGAs because PGA2 was also inhibitory, whereas PGB1, PGE1 and PGE2 were inactive. Virus adsorption and penetration do not appear to be targets of antiviral action because PGA1 substantially reduced virus replication, even when added 5 h post-infection. PGA1 did not inhibit viral reverse transcriptase, as determined by in vitro assays, suggesting that its antiviral action is not the consequence of a direct inhibitory effect on this enzyme. PGA1 also inhibited the replication of HIV-1 in CEM x 174 cells, but with less potency. Previously, intravenous infusion of PGA1 into human volunteers has shown no significant deleterious side-effects and thus these observations suggest that PGAs might have potential as antiviral agents in humans.
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PMID:Prostaglandin A inhibits replication of human immunodeficiency virus during acute infection. 194 Aug 69

The effects of various compounds were studied quantitatively on the growth of human immunodeficiency virus (HIV). For this we used a human T-cell leukemia virus type I carrying cell line, MT-4 which is most permissive for HIV infection. The results are summarized as follows: 1) Prostaglandin E2 and 12-0-tetradecanoylphorbol-13-acetate enhanced the production of HIV significantly in MT-4 cells as well as a continuous HIV producer Molt-4/HTLV-III cells. 2) Interferon gamma, retinoic acid and 3'-azido-3'-deoxythymidine inhibited the replication of HIV at the concentrations which were not cytotoxic. Mechanism of action of these compounds and its clinical implications are discussed.
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PMID:Substances affecting the infection and replication of human immunodeficiency virus (HIV). 303 Mar 46

The authors recently measured the Interleukin-1 (IL-1) and Prostaglandin E (PGE) activity of the monocyte-macrophage system (M phi) in vitro. The results indicated that immunodeficiency in cancer patients is closely associated with reduced IL-1 activity and increased PGE activity of M phi. Immunosuppressive factors in the serum of cancer patients seem to play some role in the mechanism of such change. Therefore, when potentiating M phi in nonspecific immunotherapy, it seems important to suppress secretion of PGE (a suppressor factor of M phi origin which is secreted simultaneously) to make this therapy more effective in advanced cancer cases. Based on these results, an animal experiment was carried out in which tumor-bearing mice were treated with OK-432 and Indomethacin (Ind.) (a PG inhibitor). The results of this experiment suggested that this combination therapy reinforces the M phi-mediated immunopotentiation, resulting in a stronger antitumor effect of OK-432. When we used this combination therapy in advanced cancer cases, the changes observed in immunological parameters also indicated an immunopotentiating effect, i.e., an antitumor effect. These results indicate that the optimum application of BRM therapy should be decided on the basis of an understanding of the immunological factors in the patient.
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PMID:Immunomodulating capacity of the monocyte-macrophage system in patients with uterine cervical cancer. 326 Feb 61

Hypoimmunity after major trauma and thermal injury appears to predispose to septicemia. An increase of immune suppressive T cells and the inhibitory monocytes product PGE2 has been demonstrated postburn and are suggested as contributing to postburn hypoimmunity. TP5, the biologically active part of thymopoientin, has an immunomodulating effect on T cells. Indomethacin, an irreversible blocker of the prostaglandin synthesis has been suggested to reduce the inhibitory monocytes-mediated immunosuppression. In this study strains 2 and 13 guinea pigs received 20-30% TBSA scald burn and were subsequently injected with either TP5 or indomethacin or a combination of both on the 3 following days postburn. The ability of splenocytes to produce a secondary immune response to SRBC was measured in the in vitro AFC assay. The animals who had received TP5 and indomethacin showed significant improvement in their ability to mount an immune response in the AFC assay.
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PMID:The immunomodulating effect of TP5 and indomethacin in burn-induced hypoimmunity. 623 2

Prostaglandin E2 is observed at elevated levels during human immunodeficiency virus (HIV) infection and thus may contribute to the HIV-dependent immunosuppression. The mechanisms responsible for this increase are not understood. Evidence indicates that the viral envelope proteins perturb membrane signaling mediated by the CD4 receptor, suggesting that the free envelope protein and/or the intact virus may be responsible for the increase in prostaglandin E2 levels. In this study, we have used THP-1 human monocytes and THP-1 cells differentiated by 12-O-tetradecanoylphorbol-13-acetate treatment into macrophages to determine if the HIV envelope protein, gp120, or an anti-CD4 receptor antibody stimulates prostaglandin formation by interacting with the CD4 receptor. Incubation of THP-1 cells with OKT4A antibody greatly stimulated the CD4-p56lck receptor complex as estimated by enhanced p56lck autophosphorylation, while the gp120 gave small but significant responses. Monocytic THP-1 cells poorly metabolized arachidonic acid to prostaglandin E2 and thromboxane B2 as measured by high-pressure liquid chromatography analysis. Western blot (immunoblot) and Northern (RNA) blot analyses revealed that unstimulated monocytes expressed little prostaglandin H synthase 1 and 2 (PGHS-1 and -2). Incubation of the monocytes with lipopolysaccharide, OKT4A, or gp120 did not increase the formation of prostaglandins. The expression of PGHS-1 or PGHS-2 was also not increased. Differentiation of the monocytes to macrophages by 12-O-tetradecanoylphorbol-13-acetate treatment resulted in increased expression of PGHS-1 and increased formation of prostaglandins compared with that for the monocytes. Lipopolysaccharide stimulation of the macrophages increased the formation of prostaglandins and increased the expression of PGHS-2 in the macrophages. However, OKT4A or gp120 preparation, at concentrations that stimulated p56lck autophosphorylation, did not enhance the formation of prostaglandins or the expression of PGHS-1 or PGHS-2. OKT4A and gp120 also did not stimulate the release of arachidonic acid, indicating that phospholipase A2 was not activated by the CD4 receptor in either the THP-1 monocytes or macrophages. These results indicate that activation of the CD4-p56lck receptor signal transduction pathway by the HIV envelope protein does not increase prostaglandin formation.
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PMID:Human immunodeficiency virus type 1 envelope protein does not stimulate either prostaglandin formation or the expression of prostaglandin H synthase in THP-1 human monocytes/macrophages. 749 15

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disorder characterized by increased serum immunoglobulin E levels. Bone fragility is part of this syndrome, which has recently been reported to be also associated with an imbalance in cytokine-secreting lymphocyte subpopulation. It has recently been shown that some cytokines can play a role in the bone fragility following menopause. We therefore investigated six patients (mean age 16.5 +/- 8.5 years) affected by this rare syndrome in order to study their bone remodeling and the possible involvement of cytokines in causing the bone fragility associated with this disease. Three of six patients had suffered long bone fractures; in four of six patients the cortical bone mass measured at the distal radius was two standard deviations below that of the aged-matched controls. Urinary pyridinoline excretion, a marker of bone resorption, was markedly increased in the two youngest patients. Adherent mononuclear cells derived from these patients were cultured in vitro and the bone resorbing activity (BRA) of the culture supernatant was measured by means of a fetal rat long bone assay. The BRA was up to 28% above the basal value. We compared the BRA and the cytokine production by the mononuclear cells of these patients to that of postmenopausal women. The BRA, and the IL1 beta, IL6, and TNF alpha levels in the mononuclear cell culture supernatants were identical for both HIES and postmenopausal women. However, the levels of PGE2 were higher and the levels of interferon-gamma were lower in the HIES patients. In conclusion, increased bone resorption in young patients with the HIES is responsible for the cortical bone loss that leads to a higher incidence of fractures. The high BRA secreted by the mononuclear cells of these patients is similar to that found in mononuclear cells from postmenopausal women. These data provide evidence of potent mononuclear cell activation leading to bone loss in HIES, which could be related to IgE-dependent mechanisms.
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PMID:Cytokine-mediated bone resorption in patients with the hyperimmunoglobulin E syndrome. 760 71

We investigated the hypothesis that exposure of monocytes to human immunodeficiency virus (HIV) augments production of proinflammatory mediators. The production of tumour necrosis factor alpha (TNF-alpha) and the eicosanoids PGE2 and LTB4 from human monocytes was evaluated after exposure to two strains of HIV (SSI-002 or HIV-1IIIB). After 16 h incubation with low doses of SSI-002, lipopolysaccharide-stimulated TNF-alpha production was enhanced 70-85% while PGE2 production was decreased. Heat-inactivated virus failed to alter the production of these mediators. Higher viral doses tended to decrease TNF-alpha and PGE2 production concomitantly, but this might be due to toxicity. HIV-1IIIB had no effect on either TNF-alpha or PGE2 production. Calcium ionophore-stimulated LTB4 production was doubled by HIV-1IIIB, but significantly decreased by SSI-002. Three or seven days after exposure to both HIV strains, increased PGE2 production was found. In conclusion, HIV only modestly altered the production of mediators from monocytes. The effects were strain-specific. In most experiments a second stimulus was required to demonstrate differences.
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PMID:Tumour necrosis factor and eicosanoid production from monocytes exposed to HIV in vitro. 794 62

Prostaglandin E2 (PGE2) appears to have an immunosuppressive role in human immunodeficiency virus (HIV) infection. Therefore, the effect was studied of PGE2 pretreatment of T lymphocytes from patients with lymphadenopathy associated syndrome (LAS) on the expression of CD25 and CD71 as well as plaque forming cell (PFC) generation in pokeweed mitogen (PWM)-driven cultures. The PGE2-treated or untreated T lymphocytes were cultured with B cells and monocytes in the presence of PWM. Both CD25 and CD71 expression were assessed with an immunofluorescence technique; PFC generation was tested by hemolysis. Before exposure to PWM, LAS lymphocytes showed activation as evidenced by high CD25 and CD71 expression and PFC generation. Pretreatment by PGE2 did not inhibit expression of activation markers and PFC generation in LAS cultures, in contrast to what happened in control cultures. Thus, LAS lymphocytes are activated in vivo and are less sensitive to PGE2 inhibition than normal lymphocytes.
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PMID:Impairment of lymphocyte sensitivity to prostaglandin E2 in cultures from patients with lymphoadenopathy associated syndrome. 823 82

The cytotoxic effects of the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 were studied in human CHP100 neuroblastoma cell cultures. Incubation of neuroblastoma cultures with gp120 (1 pM-10 nM) induces cell death which is not concentration-related. The significant cell death evoked by 10 pM gp120 was prevented by neutralization of the viral protein with a monoclonal anti-gp120 (IgG) antibody. In addition, gp120-induced cytotoxicity was inhibited by [DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] (CGP37849; 100 microM), [(+/-)-3R*, 4as*, 6R*, 8aR*-6-(phosphonomethyl) decahydro-isoquinoline-3-carboxylic acid] (LY274614; 100 microM), MK801 (dizocilpine; 200 nM) and 7-chloro kynurenic acid (100 microM), selective antagonists of the NMDA receptor complex; by contrast, (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 100 microM), a non-NMDA antagonist, was ineffective. Prevention of the lethality elicited by the HIV-1 coat protein was also obtained by incubating neuroblastoma cells with gp120 in Ca(2+)-free medium. The lethal effects induced by gp120 involve activation of L-arginine-nitric oxide (NO) pathway since these were prevented by haemoglobin (10 microM), a NO-trapping agent, and by D-arginine (1 mM), the less active enantiomer of the endogenous precursor of NO synthesis. Cytoprotection was also afforded by N omega-nitro-L-arginine methyl ester (L-NAME; 200 microM), an inhibitor of NO synthase, and this was reversed by L-arginine (1 mM). Interestingly, indomethacin and flufenamic acid (10 microM), two inhibitors of cyclooxygenase, protected neuroblastoma cells from death induced by gp120. Furthermore, indomethacin prevented the neuroblastoma cell death evoked by exposure of cultures to sodium nitroprusside (SNP; 0.2-1.6 mM), a NO donor. Finally significant cytotoxic effects were observed after incubation of neuroblastoma cells with prostaglandin E2 (0.1-10 microM). In conclusion, the present data suggest that death of human CHP100 neuroblastoma cells in culture produced by gp120 involves NO and PGE2 production.
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PMID:Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is prevented by NMDA receptor antagonists and inhibitors of nitric oxide and cyclooxygenase. 858 64


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