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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organisms belonging to the Mycobacterium avium complex (MAC) are common pathogens in immunosuppressed and AIDS patients. This paper reviews the role of cytokines in the pathogenesis of MAC infection. MAC organisms mainly infect monocytes and macrophages, and the effect of HIV infection on susceptibility of macrophages to MAC infection is largely unknown. Both GM-CSF and tumour necrosis factor-alpha can induce mycobacteriostatic/mycobactericidal activity in MAC-infected macrophages. The activity of interferon-gamma on mycobacterial infection appears to be dependent on the type of macrophage: in murine peritoneal and human monocyte-derived macrophages, interferon-gamma does not inhibit the intracellular growth of MAC, whereas in intestinal macrophages interferon-gamma results in inhibition of MAC. Transforming growth factor-beta 1, interleukin-10 and interleukin-6 have all been shown to counteract the immunoactivating cytokines and MAC survival may be due to induction of these inhibitory cytokines within the macrophage. GM-CSF has been given to patients with disseminated MAC infection. Isolated macrophages from these patients demonstrated increased superoxide anion production and enhanced mycobacteriostatic/cidal activity compared with macrophages isolated from the same patients before GM-CSF treatment. These results suggest that GM-CSF may have potential in the treatment of MAC infection.
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PMID:Potential role of cytokines in disseminated mycobacterial infections. 787 49

The efficacy and safety of a combination of ganciclovir plus GM-CSF was evaluated in AIDS patients with cytomegalovirus retinitis. In phase A, patients were randomized to receive ganciclovir, 5 mg/kg every 12 h for 14 days followed by 5 mg/kg daily, with (n = 24) or without (n = 29) GM-CSF (1-8 micrograms/kg daily subcutaneously) to maintain absolute neutrophil counts between 2500 and 5000 cells/microliters. In phase B, after 16 weeks zidovudine was added to the regimen of 16 patients receiving ganciclovir plus GM-CSF and 20 receiving ganciclovir alone. At this stage, GM-CSF was added to the treatment protocol of any patient receiving ganciclovir plus zidovudine who became neutropenic. In phase A, patients in the ganciclovir plus GM-CSF group had significantly higher neutrophil counts than ganciclovir-alone patients (p = 0.0001). Overall, 12.5% of patients treated with GM-CSF developed neutropenia (absolute neutrophil counts < 500/microliters phase A and < 750/microliters phase B) compared with 45% of patients treated without GM-CSF. GM-CSF patients missed 10 of a possible 4705 scheduled doses of ganciclovir compared with 34 missed doses of a possible 6584 in the ganciclovir-alone group (p = 0.011). There was a trend, although not statistically significant, for patients in the GM-CSF group to experience delayed progression of their retinitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. The ACTG 073 Team. 787 51

Haemopoiesis is often depressed in patients suffering from acquired immune deficiency syndrome (AIDS). Although several mechanisms have been postulated to be responsible for depressed haemopoiesis in AIDS patients, the aetiology of this disorder is still unknown. We hypothesized that failure of the stromal microenvironment may account for part of the haemopoietic defect observed in patients with AIDS. We therefore studied a murine model of AIDS (MAIDS) caused by infection with LP-BM5 virus to determine the ability of bone marrow cells from immunodeficient mice to establish long-term stromal cultures. In addition, normal and MAIDS mice received AZT (2 mg/ml) in their drinking water for up to 1 month to determine the effects of AZT treatment in vivo on the ability of bone marrow cells to support haemopoiesis in long-term cultures. Decreased numbers of non-adherent cells were observed in long-term bone marrow cultures (LTBMC) of MAIDS mice when compared to cultures derived from normal mice. Decreased numbers of non-adherent cells were observed in cultures of bone marrow cells from AZT-treated normal mice, when compared to untreated normal controls. Cells from AZT-treated MAIDS mice produced the smallest number of non-adherent cells. BFU-E and CFU-G/M were decreased in cultures of MAIDS mice when compared to those of normal mice. AZT-treatment further decreased the number of colony-forming cells in both MAIDS mice and normal cultures. Stromal cell function of MAIDS mice was also assessed by inoculating non-adherent cells from normal mice onto confluent irradiated MAIDS LTBMC. Stroma from MAIDS mice was unable to support haemopoietic function of normal bone marrow cells. Polymerase chain reaction (PCR) analysis of steady state levels of cytokine mRNAs of cells from confluent cultures revealed that levels of interleukin-6 mRNA were unchanged in MAIDS mice, as compared to normal controls, but the levels of GM-CSF were decreased in MAIDS mice. These data suggest that LP-BM5 MuLV infection alters the functioning of the haemopoietic stroma and that one mechanism of this depression in haemopoiesis may be via alterations of cytokine production.
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PMID:Impaired ability of bone marrow cells from immunodeficient mice to establish long-term cultures. 791 27

Drug-related neutropenia is a common observation in AIDS patients. Haematological growth factors are therefore increasingly used in combination with myelotoxic agents to reduce the risk of infection and to improve the haematological tolerance of these regimens. We report a case of an AIDS patient with Kaposi's sarcoma who received GM-CSF for severe neutropenia due to anti-tumour chemotherapy combining alpha-interferon 2b and zidovudine. During GM-CSF administration there was a marked increase in the size of the Kaposi's sarcoma lesions as confirmed by ultrasonographic examination. As GM-CSF in vitro has been shown to promote Kaposi's sarcoma-like cell cultures, we discuss the potential role of this growth factor in increasing Kaposi's sarcoma lesions in vivo.
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PMID:Possible role of granulocyte-macrophage colony stimulating factor (GM-CSF) on the rapid progression of AIDS-related Kaposi's sarcoma lesions in vivo. 794 90

The results of clinical trials suggest that human hematopoietic factors are very usefull in overcoming neutropenia. Particularly, the great clinical benefit after G-CSF, GM-CSF therapy is observed in different types of neutropenia (cyclic, chronic neutropenia) aplastic anaemia, and neutropenias in infection diseases. At present, in acquired immunodeficiency syndrome, GM-CSF and other CSFs are envisioned in a primarily adjunctive role, supporting blood counts during period of myelosuppressive drug therapy.
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PMID:[Use of hematopoietic growth factors in nonmalignant neutropenias in adults]. 806 1

A 25-year-old woman with AIDS was submitted to HLA-identical allogeneic BMT after cytoablation with busulphan and cyclophosphamide and combined anti-HIV-1 therapy with zidovudine, IFN-alpha 2 and anti-HIV-1-specific T cell clones. Marrow engraftment occurred after 18 days and tests for HIV-1 were negative after 30 days but the hematologic reconstitution of the patient was poor. A second BM infusion from the same donor was ineffective and treatment with GM-CSF only induced a transient increase of the blood cell count, suggesting iatrogenic damage to the BM microenvironment. The development of ARDS led to the death of the patient 10 months after transplantation. Post-mortem investigation did not reveal any active infections and PCR on autopsy tissues was negative for HIV-1.
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PMID:Allogeneic bone marrow transplantation combined with multiple anti-HIV-1 treatment in a case of AIDS. 813 53

3'-azido-3'-deoxythymidine (AZT), the main antiviral drug used in AIDS treatment, is known to induce anemia and neutropenia. These effects have been attributed to its toxicity to hematopoietic progenitors. In this report, we present a new approach to reduce AZT hematotoxicity by using an inhibitory factor of the hematopoietic stem cells, the tetrapeptide AcSerAspLysPro (AcSDKP, Seraspenide), which has been shown to increase the survival of mice subjected to high doses of chemotherapy and to block reversibly the cycling of human granulocyte-macrophage colony forming unit (CFU-GM) and burst forming unit erythroid (BFU-E) progenitors. Normal bone marrow mononuclear cells (BMMNC) from 14 subjects were incubated with or without AcSDKP (10(-10) M) for 20 h and with or without AZT (100 microM) for another 2 h. After washing, cells were plated in methylcellulose in the presence of interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and erythropoietin (EPO). Under these conditions, the preincubation of cells with AcSDKP reduced significantly the toxicity of AZT to both BFU-E and CFU-GM at least in 3 out of 8 and 4 out of 10 cases, respectively. A careful statistical analysis of these observations indicates that AcSDKP may be an efficient factor in preserving progenitors against AZT-induced hematopoietic toxicity.
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PMID:The tetrapeptide AcSerAspLysPro (Seraspenide), a hematopoietic inhibitor, may reduce the in vitro toxicity of 3'-azido-3'-deoxythymidine to human hematopoietic progenitors. 824 56

A mannoprotein fraction (MP-F2: mannan, > 90%; protein, 4.5%) from the human commensal microorganism Candida albicans was as efficient as interleukin-2 (IL-2) in generating cytotoxicity against the uninfected or human immunodeficiency virus type-1 (HIV-1) persistently infected monocytoid U937 cell line in cultured peripheral blood mononuclear cells (PBMC) from healthy human subjects. MP-F2-activated killing of U937 cells (U937-MAK) decreased progressively with advancing stages of HIV-1 infection to virtually no killing effect in PBMC from advanced AIDS subjects (AIDS PBMC). This decrease paralleled a lowered susceptibility of U937 cells to natural killer cell activity. In contrast, IL-2-activated killing of U937 cells (U937-LAK) was not affected by the progression of HIV infection and persisted at high levels in AIDS PBMC. To shed light on the mechanisms of U937-MAK and its decrease during HIV infection, IL-1 beta, IL-6, TNF-alpha, GM-CSF, and IFN-gamma production was analyzed. Decreases in TNF-alpha, GM-CSF, and IFN-gamma, but not IL-1 beta or IL-6, levels were observed in MP-F2-stimulated PBMC from HIV-infected subjects, compared to healthy controls. Interestingly, these cytokine levels fell before the onset of AIDS. The greatest relative drop was that of IFN-gamma, from 4600 (+/- 600) to 290 (+/- 160) and 217 (+/- 110) mean pg/ml (+/- SE) in PBMC from healthy donors (11 subjects), CDC stages II + III (14 subjects), and CDC stage IV (10 subjects), respectively. The following observations suggest that decreased IFN-gamma production plays a role in the abrogation of U937-MAK activity: (i) addition of neutralizing anti-IFN-gamma antibodies abolished both IFN-gamma and U937-MAK activity in PBMC from healthy subjects; (ii) substantial levels of IFN-gamma were detected in supernatants of PBMC cultures stimulated by IL-2, in line with preserved U937-LAK activity. Interestingly, anti-IFN-gamma antibodies also abolished TNF-alpha production, and the anti-TNF-alpha antiserum effect was comparable to that of anti-IFN-gamma in U937-MAK inhibition. In contrast, anti-TNF-alpha antibodies abrogated TNF-alpha activity, but only partially reduced IFN-gamma production. Thus, in human PBMC, U937-MAK activity progressively decreases with advancing stages of HIV infection, whereas U937-LAK activity is sustained. Furthermore, the present results indicate a pivotal role for IFN-gamma in U937 MAK activity, possibly through activation of TNF-alpha production.
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PMID:Mannoprotein-induced anti-U937 cell cytotoxicity in peripheral blood mononuclear cells from uninfected or HIV-infected subjects: role of interferon-gamma and tumor necrosis factor-alpha. 825 54

Human immunodeficiency virus (HIV), is able to replicate in many human cells such as helper lymphocytes, monocytes/macrophages and glial cells. Monocytes/macrophages must be considered an important reservoir of HIV in vivo and a producer of cytokines such as Interleukin-1 (IL1) and tumor necrosis factor (TNF). These substances lead to an autocrine feedback loop that produces an increased virus replication and a secondary induction of other cytokines such as Interleukin 6 (IL6) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cytokines all together may be responsible for many clinical aspects of the disease such as headache, fever, anorexia, subtle cognitive changes, motor disfunctions and cachexia. The future strategies in the treatment of AIDS must be a combination of drugs acting on different points of viral replication and with synergistic potential. Omega 3 polyunsaturated fatty acids (omega-3) can be considered a candidate for their pleiotropic effects on immunological and metabolic systems. In particular, their use is considered for their ability to decrease IL1 and TNF production by monocytes/macrophages, as demonstrated by many authors. The decreased induction of these cytokines and consequently of IL6 and acute phase proteins may have beneficial effects on many clinical manifestations of AIDS such as cachexia.
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PMID:Omega-3 fatty acids as coadjuvant treatment in AIDS. 828 91

The expression of human immunodeficiency virus type 1 (HIV-1) is enhanced after cell activation because of the interaction of cell-encoded nuclear factors that interact with binding sites in the long terminal repeats (LTRs). Here we studied the contribution of cell type-specific activation signals to differences in cytotropism of HIV-1 variants. Four closely related molecular HIV-1 clones with distinct biological phenotypes and different capacities to replicate in primary monocyte-derived macrophages (MDMs) or T cell lines were used. Sequence analysis of these LTRs revealed variation in functionally important regions. Adaptation of virus variants to particular host cells by differences in LTR responsiveness was analyzed. LTR-CAT constructs were transiently transfected in T cells that were stimulated with T cell-specific activation signals such as combinations of anti-CD3 or anti-CD28 MoAB or in primary monocytes that were stimulated with IL-3, IL-4, or GM-CSF. No differences in responsiveness to cell type-specific signals were demonstrated. To further elucidate the level of restriction in cell tropism, transfection of four full-length infectious molecular HIV-1 clones into 5-day cultured MDMs was performed. From all clones, competent virus could be rescued from MDMs by coculture with PHA-stimulated PBLs. However, following cell-free inoculation, proviral DNA could be detected by PCR analysis only in monocytes exposed to HIV-1 clones that previously were shown to establish productive infection.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Res Hum Retroviruses 1993 Jul
PMID:Early replication steps but not cell type-specific signalling of the viral long terminal repeat determine HIV-1 monocytotropism. 836 71


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