Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T-cell adjuvancy involves the use of agents to stimulate preferentially delayed type hypersensitivity (DTH). Traditional adjuvants like Alum, Freunds, muramyl peptides, and endotoxins are not selective. Natural infection (e.g. vaccinia) may yield selective DTH. Low dose cyclophosphamide (CY) with mycobacteria was the first experimental T-cell adjuvant. New adjuvant formulations (ISCOMS, MAPS, etc.) with synthetic T-cell epitopes offer improved formulations. Upregulation of TH-1 helper cells and their actions with interleukins like IL-2, IL-12, and gamma IFN or antibodies to IL-4 and IL-10 may augment potently pathogen and tumor resistance. Similarly, transfection of tumor target cells with genes for IL-2, IL-12, gamma IFN, etc., offers novel vaccine treatment approaches. Finally, "thymomimetic" peptides like thymosin alpha 1 or drugs like levamisole or isoprinosine alone or in conjunction with interleukins may augment TH-1 and DTH responses. These approaches are seeing increasing emphasis in new treatment strategies for cancer and infections like HIV.
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PMID:T-cell adjuvants. 780 29

Different experimental approaches were used to prove or disprove the "TH1/TH2 switch theory" of HIV-infection. No increase, or even a decrease, in the production of TH2-type cytokines (IL-4, IL-5, and IL-10) by either bulk circulating mononuclear cells or CD4+ T-cell clones generated by PHA stimulation of single T cells from HIV-infected individuals in all stages of disease compared to HIV-negative donors was observed. However, enhanced proportions of CD4+ T-cell clones able to produce both TH1-type and TH2-type cytokines (TH0 clones) were derived from either skin-infiltrating, in vivo-activated, T cells or in vitro antigen-stimulated peripheral blood T cells of HIV-infected individuals. Of note, TH1, TH2 and TH0 clones obtained from HIV-seronegative healthy donors showed different ability to support viral replication after infection with HIV in vitro. All TH2 and most TH0 clones supported HIV replication efficiently, whereas TH1 clones did not. These results suggest preferential HIV replication in T cells producing TH2-type cytokines rather than TH1/TH2 switch in HIV infection.
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PMID:Role of TH1/TH2 cytokines in HIV infection. 782 29

During human immunodeficiency virus infection and allergic diseases, characterized by a dominant T helper (Th) 2 response, overproduction of prostaglandin E2 (PGE2) is observed. In this paper we studied the effect of PGE2 on interleukin (IL)-12 synthesis, because this cytokine has been described to be essential in induction of Th1 responses. IL-12 synthesis was induced in monocytes that were stimulated with Neisseria meningitidis-derived lipopolysaccharide in whole blood cultures. PGE2 almost completely inhibited lipopolysaccharide induced IL-12 production, whereas IL-6 production was only partially inhibited by PGE2. In contrast, the production of IL-10 was approximately twofold enhanced at these conditions. The effects of PGE2 were due to its cAMP-inducing capacity, since they could be mimicked by other cAMP inducers. Recombinant human IL-10 also inhibited IL-12 and IL-6 production. However, the inhibitory effect of PGE2 on IL-12 production was independent of IL-10 since neutralizing anti-IL-10 antibodies were unable to reverse this inhibition. These results suggest that the capacity of an antigen to induce PGE2 synthesis may play a crucial role in the development of either a Th1 or Th2 response.
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PMID:Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production. 783 30

Human interleukin 10 is a pleiotropic cytokine capable of suppressing cytokine production from macrophages and T cells; in addition, it exerts complex regulatory effects on CD8+ T cells, natural killer cells, vascular endothelial cells, and B lymphocytes. Levels of IL-10 are elevated in HIV-infected individuals, suggesting that this cytokine may play a role in the suppression of T cell and monocyte/macrophage function typical of HIV disease. In this article, IL-10 blocked HIV-induced tumor necrosis factor alpha and interleukin 6 secretion and inhibited HIV replication in monocyte-derived macrophages (MDMs). The inhibition by IL-10 was correlated with a block in endogenous TNF-alpha and IL-6 secretion from HIV-infected MDMs.
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PMID:Interleukin 10 blocks HIV replication in macrophages by inhibiting the autocrine loop of tumor necrosis factor alpha and interleukin 6 induction of virus. 784 77

HIV-1 infection and the HIV gp120 have been shown to induce an IL-10 increase in cultured peripheral blood mononuclear cells. Furthermore, the expression of this cytokine has been reported to increase in lymphnodes of infected patients along the disease course, and a shift from the TH-1 towards the TH-0/TH-2 phenotypes (with subsequent IL-10 release) has been hypothesized to underly AIDS progression. In this study the serum IL-10 levels found in 30 HIV-negative controls and in 65 HIV-positive patients, untreated with AZT and negative for HBsAg and HCV-Ab have been compared, using a commercial, competitive ELISA method based on a polyclonal anti-IL-10 serum. With this test, HIV-positive sea showed IL-10 levels significantly higher than those found in the controls. In addition the IL-10 levels progressively increased in the subsequent CDC stages, without further changes from the stage III to the stage IV. Accordingly, patients evaluated two times in CDC stage II, with a time interval of at least one year, showed significant IL-10 increases, even more pronounced when the same patients passed from CDC stage II to stage III. Furthermore, a significant, negative correlation was observed between the circulating IL-10 levels and the patients' CD4/CD8 ratios. These data may be important from a clinical point of view since IL-10 monitoring could be considered as a surrogate marker for evaluating the disease progression. In addition, several immunological abnormalities present in HIV positive patients, such as the monocyte/macrophage impairment and the hypergammaglobulinemia could be related to the enhanced IL-10 expression.
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PMID:Serum IL-10 levels in HIV-positive subjects: correlation with CDC stages. 786 12

HIV-1-infected brain macrophages participate in neurologic dysfunction through their continual secretion of neurotoxins. We previously demonstrated that astroglial cells activate HIV-1-infected monocytes to produce such neurotoxic activities. In this study, the mechanism underlying these monocyte secretory activities was unraveled and found dependent on HIV-1's ability to prime monocytes for activation. LPS stimulation of HIV-1-infected monocytes resulted in an overexpression of eicosanoids, platelet-activating factor (PAF), and TNF-alpha. This was dependent on the level of HIV-1 infection and monocyte stimulation. Cell to cell interactions between activated virus-infected monocytes and primary human astrocytes reduced monocyte secretions. The capacity of astrocytes to deactivate monocytes was, notably, TGF-beta independent. Although astrocytes constitutively produced latent TGF-beta 2, HIV-1-infected monocytes neither affected TGF-beta 2 production nor converted it into a bioactive molecule. Furthermore, addition of rTGF-beta 1 or rTGF-beta 2 or its Abs to LPS-stimulated monocyte-astrocyte mixtures had no effect on monokine production. In contrast, addition of rIL-10 to LPS-stimulated monocytes produced a dose-dependent decrease in TNF-alpha. IL-10 mRNAs were detected in monocytes, but not astrocytes, following LPS treatment. These results suggest that macrophage activation, a major component of HIV-1 infection in the brain, precipitates neuronal injury by causing virus-infected cells to synthesize neurotoxins. The neurotoxins produced by monocytes are then regulated by astrocytes. Astrocytes therefore, can play either positive or negative roles for disease depending on prior macrophage activation. These findings begin to unravel the cellular control mechanisms that influence cognitive and motor dysfunctions in HIV-1-infected individuals.
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PMID:A regulatory role for astrocytes in HIV-1 encephalitis. An overexpression of eicosanoids, platelet-activating factor, and tumor necrosis factor-alpha by activated HIV-1-infected monocytes is attenuated by primary human astrocytes. 789 36

Peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients, asymptomatic or with acquired immunodeficiency virus, produced 10-fold less interleukin 12 (IL-12) free heavy chain and fivefold less biologically active IL-12 heterodimer than PBMC from uninfected healthy donors when challenged in vitro with the common human pathogen Staphylococcus aureus. In contrast, PBMC from HIV-infected individuals and uninfected control donors produced similar levels of tumor necrosis factor alpha, IL-1 beta, and IL-10, and PBMC from HIV-infected individuals produced three- to fourfold more IL-6 compared with PBMC from uninfected control donors. The defect in IL-12 production is not due to hyperproduction of IL-10, a cytokine exerting an autocrine-negative feedback on IL-12 production, but was directly related to HIV infection, as suggested by the reduced ability of monocytes infected in vitro with HIV to produce IL-12. IL-12 deficiency may be an important component of the immunodeficiency associated with HIV infection.
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PMID:Impaired interleukin 12 production in human immunodeficiency virus-infected patients. 790 24

AIDS typically consists of three phases: (1) an acute, infectious mononucleosis-like syndrome followed by (2) a prolonged asymptomatic stage ending in (3) the appearance of frank AIDS. The asymptomatic phase may last for years and its presence suggests a persistent conflagration between the virus and the host's immune response. There is considerable evidence that an immune response develops but the response is ultimately inadequate. From the work of others as well as our own, we have constructed a hypothesis which attempts to explain some aspects of the immune response. We propose that HIV-1 preferentially infects a subset of CD4+ lymphocytes which are then either destroyed or altered in their biological functions. Further, we suggest that this subset represents the CD4+ TH1 lymphocyte population. By decreasing the quantity of IL-2 and interferon-gamma produced by TH1 lymphocytes, the production of cytokines by TH2 cells is increased. One of the cytokines produced by TH2 lymphocytes is IL-10, a polypeptide with significant inhibitory properties towards lymphocytes. Sera from patients with frank AIDS have significant lymphocyte inhibitory activities some of which operate through IL-10. Thus, a gradual shift to a TH2-type response and release of increasing amounts of inhibitors eventually prevents the host from replacing destroyed cells or mounting new and appropriate immune responses.
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PMID:Breaking the asymptomatic phase of HIV-1 infection. 791 Jun 37

CD8+ T cells activated in the presence of IL-4 can develop into distinct, non-cytotoxic CD8- and cytotoxic CD8+ subsets that produce IL-4, IL-5, IL-10 but do not produce IFN-gamma. These 'Th2 like' CD8+ cells may enhance Th2 responses, help B cells or suppress Th1 immune responses. Importantly, the switch from the cytotoxic, IFN-gamma producing CD8+ T-cell phenotype could compromise the host response to infectious agents such as HIV.
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PMID:Non-cytotoxic, IL-4, IL-5, IL-10 producing CD8+ T cells: their activation and effector functions. 791 14

Human immunodeficiency virus infection leads to a deregulated production of a number of cytokines. Some of them (IL-1, IL-6, TNF-alpha, interferon-gamma) are produced in increased amounts in vivo, whereas the production of IL-2 is decreased. This latter abnormality plays a pivotal role in the establishment of the immunodeficiency. Some cytokines (IL-1, IL-6, TNF-alpha) stimulate the in vitro replication of HIV, whereas others (mainly the interferons) inhibit it. The effect of cytokines in vivo in the spreading of HIV remains, however, largely unknown. Cytokines may also be involved in the development of many clinical manifestations associated with HIV infection. IL-1, IL-6 and TNF-alpha may play a role in tissue damages associated with opportunistic infections, in HIV-related encephalopathy and in cachexia. Cytokines, mainly IL-6, IL-10 and IL-13, may stimulate the growth of malignant cells during Kaposi sarcoma or lymphomas. Better knowledge of the role of cytokines during HIV infection should allow new therapeutic approaches based on the use of either recombinant cytokines or specific antagonists, with the aim of limiting both HIV spreading and the clinical manifestations of this infection.
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PMID:Cytokines in HIV infection. 792 84


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