Biotherapy

, Volume 8, Issue 3–4, pp 243–249 | Cite as

Cytokines and the immune response

  • P. H. Van der Meide
  • H. Schellekens

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.

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Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • P. H. Van der Meide
    • 1
  • H. Schellekens
    • 2
  1. 1.Biomedical Primate Research CentreBPRCRijswijkThe Netherlands
  2. 2.Diagnostic Centre SSDZDelftThe Netherlands

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