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Query: HUMANGGP:031927 (cytokine)
 144,509 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Promonocytic cells U937 with previously established HIV-1 persistent infection, were treated with increasing doses of the recombinant INF-alpha 2. This resulted in a significant decrease of virion-associated reverse transcriptase levels in medium of the cultures studied, most pronounced by the highest interferon doses, but depending on this cytokine presence. In spite of the marked restrictive effect of the interferon on the infectious virus production the synthesis, of viral structural proteins by the U937 cells, as detected by immunofluorescence, was not affected. The therapeutic index of interferon was considerably high.
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PMID:Recombinant interferon-alpha 2 inhibits HIV replication in chronically infected promonocytic cells. 127 64

Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-alpha, transforming growth factor-beta and interferon-gamma have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia (< 750 cells/microliters), who were treated concomitantly with recombinant human G-CSF (3-4 micrograms subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Life-threatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted.
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PMID:Granulocyte colony-stimulating factor treatment in AIDS patients. 128 Apr 96

Monocyte/macrophage-mediated tumor cytotoxicity was studied in patients infected with human immunodeficiency virus-1 (HIV-1) at various stages [Center for disease control (CDC) classification] of the disease. using the P-815 tumor cell line as target cells, the results demonstrated reduced monocyte/macrophage cytotoxicity early in HIV-1-related disease (CDCIII, P < 0.01). This cellular dysfunction sustained during the progression of the disease. Evidence could be presented that neither exogenous application of macrophage-stimulating cytokines (e.g. interferons) nor their endogenous induction in vitro restored monocyte/macrophage cytotoxicity. However, enhanced tumor necrosis factor (TNF)-alpha production, which parallels the observed reduced capacity to lyse P-815 tumor cells, might be the major source for monocyte/macrophage-mediated cell lysis. TNF-alpha-induced cytotoxicity can be inhibited by addition of anti-TNF-alpha. Other experimental models using TNF-sensitive tumor target cells may, therefore, mimic monocyte/macrophage-mediated lysis. Suppression of monocyte/macrophage cytotoxicity in later stages of HIV-1 infection (AIDS-related complex, AIDS) could partly be reverted by treatment with the cyclooxygenase blocker, indomethacin. The responsible arachidonic acid product mediating suppression was found to be prostaglandin E2, suggesting that in addition to the direct viral interference cellular dysfunction is at least in part a result of altered cytokine regulation.
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PMID:Cytokine-mediated regulation of monocyte/macrophage cytotoxicity in human immunodeficiency virus-1 infection. 128 2

Peyer's patch (PP) T cells through the production of appropriate cytokines foster the development of immunity to the intestinal protozoan parasites such as Giardia. T cell destruction by the human immunodeficiency virus precedes the development of acquired immune deficiency syndrome. Thus, HIV may increase susceptibility to intestinal parasite infections. Therefore, we measured the resistance and T cell cytokine responses to Giardia in C57B1/6 mice infected with the retrovirus LP-BM5 which produces a murine AIDS (MAIDS). Mice with MAIDS and controls were intragastrically challenged with 1 x 10(5) G. muris cysts. Fecal counts were measured weekly following challenge. Also, PP T cell production of interleukin (IL)2, IL3, IL4, and Interferon-gamma in response to G. muris trophozoite antigens displayed on antigen presenting cells were measured at these times. Prior to day 14 of the infection, the number of Giardia cysts in the retrovirus group paralleled that in controls. However, by day 21 after Giardia infection, mice with MAIDS failed to clear the Giardia cysts from the intestine while the control mice were completely free of cysts. IL2 and IL4 production in response to Giardia trophozoites by unfractionated PP lymphocytes were severely depressed in the retrovirus infected group, while IFN-gamma production was increased. Depressed cytokine production was most likely due to depressed PP T cell numbers. When fractionated enriched T cells were adjusted to a uniform concentration in in vitro immunization cultures, the production of IL2 and IL4/IL5 were similar between retrovirus infected compared with control mice. Recoverable PP T cells were lower in mice with MAIDS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppression of resistance to Giardia muris and cytokine production in a murine model of acquired immune deficiency syndrome. 129 11

Primary cultures of human embryonic neurons and astrocytes have been used to test the interactions between neural cells and either human immunodeficiency virus type 1 (HIV-1) or HIV-1-infected monocytes. After direct infection with HIV-1, neither morphological alteration of neurons and astrocytes nor signs of viral replication were observed. Similarly, cultured human neurons and astrocytes were resistant to incubation with the supernatant of HIV-1-infected U937 cells, a human monoblastoid cell line. In contrast, HIV-1-infected U937 monocytic cells adhered to neural cells and induced large plaques of necrosis surrounding them. This cytopathic effect began at the time of viral replication (day 16 after infection). Its intensity depended on that of viral replication, and its range was identical to the region of diffusion of viral antigens, as judged by immunocytochemistry. The cytopathic effect was not dependent on the release of free radicals. It could not be induced by cytokines or cytokine-stimulated U937 cells. It is likely that this cytopathic effect depends on the release of viral antigens either within the site of adherence itself or within close range of the astrocyte membrane.
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PMID:Human immunodeficiency virus type 1-infected monocytic cells can destroy human neural cells after cell-to-cell adhesion. 843 89

Human cytomegalovirus (HCMV) is a potential cofactor in HIV-1 infection. To investigate the mechanism whereby HCMV promotes HIV-1 replication, a PBMC coculture assay which measures HIV-1 p24 antigen release was used as an index of viral replication. HCMV-stimulated PBMC were capable of inducing HIV-1 replication in cocultures with acutely infected PBMC; however, this occurred only when the PBMC were from HCMV-seropositive donors (598 +/- 207 versus 27 +/- 10 pg/ml p24 antigen with PBMC from HCMV-seronegative donors on day 6 of coculture). Upon stimulation with HCMV, PBMC obtained exclusively from HCMV-seropositive donors released tumor necrosis factor (TNF)-alpha (270 +/- 79 pg/ml at 18 h of culture). Monoclonal antibodies to TNF-alpha blocked the activity of HCMV-stimulated PBMC in cocultures both with acutely HIV-1-infected PBMC and with the chronically infected promonocytic line U1. Also, treatment of HCMV-stimulated PBMC with pentoxifylline, an inhibitor of TNF-alpha mRNA, markedly reduced HIV-1 replication in cocultures both with acutely and chronically infected cells. These results indicate that TNF-alpha is a key mediator of HIV-1 replication induced by HCMV-stimulated PBMC and support the concept that this cytokine plays an important role in the pathogenesis of HIV-1 infection.
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PMID:Human cytomegalovirus-stimulated peripheral blood mononuclear cells induce HIV-1 replication via a tumor necrosis factor-alpha-mediated mechanism. 131 Jun 98

Infection with the human immunodeficiency virus-1 is associated with a marked increase in the incidence of Kaposi's sarcoma. Recent studies suggest that the risk of Kaposi's sarcoma in human immunodeficiency virus infection is increased with oral-fecal contact and that a sexually transmitted agent possibly related to human papillomavirus-16 could be involved. Exposure to this or another sexually transmitted agent apparently alters both the morphology and growth regulation of the Kaposi's sarcoma progenitor cells. These changes include the expression of the alpha chain of the interleukin-6 receptor with the acquisition of an interleukin-6-dependent autocrine growth loop. Subsequent perturbation of multiple cytokines during human immunodeficiency virus infection, including Oncostatin-M, interleukin-1 beta and tumor necrosis factor-alpha alters the subsequent growth of Kaposi's sarcoma. These studies suggest that control of cytokine perturbations or the underlying human immunodeficiency virus-1 infection should result in a significant reduction in the rate of growth of acquired immunodeficiency syndrome-related Kaposi's sarcoma.
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PMID:Pathogenesis of human immunodeficiency virus-related Kaposi's sarcoma. 133 10

Tumor necrosis factor is a cytokine that participates in the mediation of numerous diseases associated with inflammation, cachexia, shock, and tissue injury. Early studies of the biology of TNF delineated its hormonal actions as well as its systemic toxicity. More recent investigations have drawn attention to its paracrine actions that predominate when it is produced locally in the brain or vital organs. For instance, when compartmentalized production of TNF occurs in the central nervous system it directly mediates fever, anorexia, and altered whole-body metabolism. Since these changes are mediated within the neural network they occur independently of simultaneously sampled serum TNF levels. These paracrine actions of TNF have implications for diseases associated with production of TNF in tissues (e.g. HIV cerebritis, multiple sclerosis, cerebral malaria and cancer), because they may differ markedly from the hormone like-actions associated with systemic release. Since TNF may be beneficial in some diseases yet injurious in others, both the hormonal and paracrine actions must be precisely defined in order to formulate novel treatment strategies based on either enhancing its useful effects, or suppressing toxicity.
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PMID:Tumor necrosis factor in metabolism of disease: hormonal actions versus local tissue effects. 134 May 27

We describe a peptide vaccine model based on the mimicry of surface coat protein of a pathogen. This model used a macromolecular assemblage approach to amplify peptide antigens in liposomes or micelles. The key components of the model consisted of an oligomeric lysine scaffolding to amplify peptide antigens covalently 4-fold and a lipophilic membrane-anchoring group to further amplify noncovalently the antigens many-fold in liposomal or micellar form. A peptide antigen derived from the third variable domain of glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1), consisting of neutralizing, T-helper, and T-cytotoxic epitopes, was used in a macromolecular assemblage model (HIV-1 linear peptide amino acid sequence 308-331 in a tetravalent multiple antigen peptide system linked to tripalmitoyl-S-glycerylcysteine). The latter complex, in liposome or micelle, was used to immunize mice and guinea pigs without any adjuvant and found to induce gp120-specific antibodies that neutralize virus infectivity in vitro, elicit cytokine production, and prime CD8+ cytotoxic T lymphocytes in vivo. Our results show that the macromolecular assemblage approach bears immunological mimicry of the gp120 of HIV virus and may lead to useful vaccines against HIV infection.
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PMID:Macromolecular assemblage in the design of a synthetic AIDS vaccine. 134 73

The mechanism for the gradual loss of CD4+ T lymphocytes and the development of the slowly progressive inflammatory/degenerative lesions that accompany human immunodeficiency virus infection are poorly understood. Using the Simian immunodeficiency virus (SIVmac) macaque model of AIDS, we found that persistently infected primary macrophages fuse with primary activated CD4+ lymphocytes and that this interaction results in production of tumour necrosis factor-alpha (TNF alpha) and interleukin 6 (IL-6). An earlier report had shown that SIV-infected macaque macrophages fuse with CEM174 cells (a human CD4+ cell line) and cause their lysis. In the present report, we have shown that TNF-alpha and IL-6 are also produced during the early stages of this interaction. Data from cocultivation of infected macrophages with several CD4+ T cell lines, including CEM174, suggested that the cytokines are produced by the T cells, and that cytokine production is restricted to those cells which not only express CD4, but are also capable of fusing with the infected macrophages. These data suggest that infected macrophages in vivo could fuse with and eliminate activated CD4+ lymphocytes and, during this interaction, release cytokines, which would contribute to the degenerative and inflammatory lesions characteristic of this disease.
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PMID:Tumour necrosis factor and interleukin 6 production during interaction between activated CD4+ lymphocytes and simian immunodeficiency virus-infected macrophages. 135 Mar 3


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