Modification of the anti-CD3-induced cytokine release syndrome by anti-interferon-gamma or anti-interleukin-6 antibody treatment: protective effects and biphasic changes in blood cytokine levels

Eur J Immunol. 1993 Sep;23(9):2209-16. doi: 10.1002/eji.1830230924.


Anti-interferon-gamma (IFN-gamma) antibodies were found to protect mice against pathological changes induced by injection of anti-CD3 antibody: incidence of diarrhea, severity of hypothermia and mortality rates were dramatically reduced. In anti-IFN-gamma antibody-treated mice, IFN-gamma blood levels were significantly reduced at 1.5 h post anti-CD3 challenge, but more elevated levels were found from 4 to 24 h. This rebound-like IFN-gamma response coincided with more profound hypoglycemia. Tumor necrosis factor and interleukin (IL)-6 levels were not affected by anti-IFN-gamma treatment. Exogenous IFN-gamma, administered within 3 h (but not later) of the anti-CD3 challenge made the syndrome worse. Furthermore, inter-mouse strain differences in sensitivity to the anti-CD3 syndrome correlated with the ability of the strain to produce IFN-gamma. Anti-IL-6 antibodies provided only marginal protection against hypothermia and mortality, but did markedly reduce hypoglycemia. Levels of biologically active IL-6 in serum were not influenced by anti-IL-6 antibody treatment during the first few hours after anti-CD3 challenge, but were significantly increased at later times. The data provide evidence that endogenous IFN-gamma is a critical element in the early phase of the anti-CD3 syndrome; endogenous IL-6, while possibly being involved in hypoglycemia, seems of lesser importance for the outcome of the syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • CD3 Complex / immunology*
  • Cricetinae
  • Cytokines / blood*
  • Cytokines / metabolism
  • Hypoglycemia / etiology
  • Hypothermia / etiology
  • Interferon-gamma / immunology
  • Interferon-gamma / physiology*
  • Interleukin-6 / immunology
  • Interleukin-6 / physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Muromonab-CD3 / immunology*
  • Muromonab-CD3 / toxicity
  • Species Specificity
  • Syndrome


  • Antibodies
  • CD3 Complex
  • Cytokines
  • Interleukin-6
  • Muromonab-CD3
  • Interferon-gamma