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Cytokines and the immune response

P H Van der Meide1, H Schellekens

  • 1Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.

Biotherapy (Dordrecht, Netherlands)
|January 1, 1996
PubMed
Summary

Cytokines like IFN-gamma and TNF-alpha play key roles in autoimmune diseases and infections. Blocking these cytokines can ameliorate disease, while their dysregulation contributes to conditions like AIDS.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Pathophysiology

Background:

  • Cytokines are crucial regulators of immune and inflammatory responses.
  • Aberrant cytokine production contributes to various diseases, including autoimmune disorders, infections, and transplant rejection.
  • Cytokines produced by CD4+ T cells are critical in determining disease outcomes.

Purpose of the Study:

  • To review the role of specific cytokines (IL-1, IL-4, IL-6, IL-10, IL-12, TNF-alpha, IFN-alpha, -beta, -gamma) in the pathophysiology of autoimmune diseases, infectious diseases, and allograft rejection.
  • To explore the impact of HIV-1 and its proteins on cytokine production and immune responses.
  • To investigate therapeutic strategies involving cytokine modulation.

Main Methods:

  • In vivo blocking experiments using monoclonal antibodies and soluble cytokine receptors.
  • Genetic manipulation, such as gene disruption (IFN-gamma R knockout mice).
  • In vitro studies on cytokine production by leukocytes, macrophages, and cell lines upon stimulation with viral proteins (gp120) or cytokines.

Main Results:

  • Interferon-gamma (IFN-gamma) blockade ameliorated experimental autoimmune diseases in rodents.
  • IFN-alpha reduced disease incidence and progression in a Myasthenia gravis mouse model.
  • Tumor Necrosis Factor-alpha (TNF-alpha) was identified as a cause of mortality in LPS-induced reactions, and it potentiated HIV-1 replication and cell death.
  • HIV-1 gp120 suppressed IFN-gamma production and induced IFN-alpha, IL-6, and TNF-alpha, contributing to AIDS neuropathology.

Conclusions:

  • IFN-gamma plays a central role in autoimmunity and its blockade is a potential therapeutic strategy.
  • Cytokine dysregulation, particularly involving IFN-gamma, TNF-alpha, and IL-12, is implicated in various pathological conditions.
  • HIV-1 interactions with cytokines contribute significantly to AIDS pathogenesis, including neuropathology and viral spread.

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