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Notes: In a pure population of rat bone marrow-derived mononuclear phagocytes (BMMø), the expression of major histocompatibility complex (MHC) molecules and ability to manifest tumoricidal activity were simultaneously studied. Resting BMMø, which express low levels of MHC class II molecules and do not manifest tumoricidal activity, become strongly MHC class II-positive, and evolve tumoricidal activity within 24 h when incubated with macrophage-activating lymphokines (MAF) or gamma interferon (IFN-γ). In contrast, BMMø which were interacted for 24 h with heat-killed microbial agents (Corynebacterium parvum, Listeria) evolve tumoricidal activity without parallel enhancement of MHC class II expression. IFN-α,β neither induced tumoricidal activity nor enhanced MHC class II expression. Further experiments have shown that (a) the kinetics of MAF- and/or IFN-γ-induced amplification of MHC class II expression and of tumoricidal activity are different; (b) enhancement of MHC class II expression by rIFN-γ is not invariably paralleled by induction of tumoricidal activity; and (c) inhibitors of macrophage tumoricidal activity differ in their ability to affect MHC class II expression. It is concluded from these findings that in a population of pure BMMø, i.e. in the complete absence of lymphocytes, the expression of MHC molecules and induction of tumoricidal activity are independently regulated phenomena; in particular, the enhanced expression of MHC class II molecules is not a prerequisite for induction and/or manifestation of tumoricidal activity by mononuclear phagocytes.

Notes: [Auszug] HDV superinfects patients with an acute or chronic hepatitis. It has been implicated in acute fulminant hepatitis B2, and, more importantly, infects chronic carriers of hepatitis B3'4. Up to 20-30% of all exacerbations of chronic carriers of HBV have been reported to be caused by hepatitis delta ...

Notes: Abstract Several factors may inhibit the activity of IFNs. Some of these occur naturally, others are therapy-induced or artificial. Naturally occurring antibodies appear to have a much broader reactivity than therapy-induced antibodies. Naturally induced antibodies are reported in patients suffering from chronic graft-versus-host disease after bone marrow transplantation. Differences in the reported immunogenicity between interferons may not be due to the minor variation in amino acid sequence. The clinical significance of therapy-induced antibodies has been unclear. In patients treated for chronic hepatitis C, antibody formation is closely related to relapse. In animal studies the efficacy of treatments targeting the IFN receptor interaction has been shown. Soluble IFN-γ receptor inhibits the development of autoimmune diseases in mice. Monoclonal antibodies to the IFN-α receptor protects against allograft rejections in monkeys. Two naturally occurring inhibitors of IFN action were reported. The clinical significance and structure of these inhibitors remain elusive.

Notes: Abstract Cytokines participate in many physiological processes including the regulation of immune and inflammatory responses. These effector molecules are produced transiently and locally controlling the amplitude and duration of the response. A variety of experiments has shown that excessive or insufficient production may significantly contribute to the pathophysiology of a range of diseases. Particularly cytokines released by CD4+ T cells at the onset of an immune response are thought to be decisive for pathological or physiological consequences. The meeting in Budapest was focussed on cytokines known to contribute to the pathophysiology of autoimmune diseases, infectious diseases and allograft rejection (e.g., IL-1, IL-4, IL-6, IL-10, IL-12, TNF-α and IFN-α,-β,-γ). A central role for IFN-γ in autoimmunity was suggested by blocking experimentsin vivo using monoclonal antibodies and soluble forms of the IFN-γ receptor (IFN-γsR). These agents ameliorated disease development in a variety of experimental autoimmune diseases in rodents. In a mouse model for the human disease Myasthenia gravis, IFN-α was found to reduce both the incidence and progression of the disease. Treatment of R. aurantiacus-infected mice with anti-IL-4 monoclonal antibodies (mAbs) was reported to interfere with the regression of granulomas in spleen and liver, most likely through inadequate IL-4-mediated suppression of IFN-γ production. In addition, it was shown that mice with disrupted IFN-γ R genes died rapidly after infection with the BCG strain of M. bovis, whereas normal mice survived the infection. IL-12 was found to be the main inductor of IFN-γ during the lethal Shwartzman reaction. TNF-α was identified as the principal cause of mortality after the second injection with LPS. In a variety of studies examining the role of cytokines in the pathogenesis of AIDS, much attention was given to thein vitro effects of HIV-1 and/or the HIV-1 viral membrane protein gp120 on triggering cytokine production by peripheral blood leukocytes (PBLs) and purified monocytes/macrophages (Mø) originating from healthy donors. Gp120 as a sole agent significantly suppressed IFN-γ production by mitogen-stimulated PBLs and induced the production of IFN-α in cultures of normal human peripheral blood mononuclear cells (PBMCs). In a human macrophage cell line, TNF-α exerted a stimulatory effect on viral replication and programmed cell death induced by HIV-1 which was potentiated by the simultaneous incubation with IFN-γ. Upon transfection of human PBLs and CD4+ T cells with a retroviral vector encoding human IFN-β, a notable reduction in reverse transcriptase activity after HIV-1 challenge was observed. Gp120 was also found to induce both IL-6 and TNF-α expression and to induce morphological changes reminiscent for apoptosis in primary astrocytes and in a re-aggregated human brain cell model, suggesting a role for these cytokines in the neuropathology of AIDS dementia. Moreover, data were presented indicating that cytokine-induced expression of cell adhesion molecules (e.g., ICAM-1) in HIV-1 infected U 937 cells leads to high level incorporation of this molecule in the membrane of the viral progeny which may play a role in the attachment of such virions to CD4-negative cells.