Elevated serum cytokines during human anaphylaxis: Identification of potential mediators of acute allergic reactions

J Allergy Clin Immunol. 2009 Oct;124(4):786-92.e4. doi: 10.1016/j.jaci.2009.07.055. Epub 2009 Sep 19.


Background: Anaphylaxis is generally unanticipated and requires emergency management. Therefore, the biological mediators in human beings have been difficult to define.

Objective: Our aim was to identify cytokines and chemokines whose concentrations increase during anaphylaxis in human beings and to determine how each correlates with severity.

Methods: We measured the concentrations of potential mediators, including cytokines, chemokines, mast cell tryptase (MCT), and histamine, over 3 time points in 76 patients presenting to emergency departments with anaphylaxis and correlated these with a global severity scale, hypotension, and hypoxia.

Results: IL-2, IL-6, IL-10, TNF receptor I, MCT, and histamine were significantly elevated in patients with severe reactions (n = 36) compared with moderate reactions (n = 40) and healthy controls. Histamine levels peaked at emergency department arrival, whereas other mediators peaked later. IL-4, IL-5, IL-13, IFN-gamma, and TNF-alpha were marginally elevated in severe reactions compared with healthy controls but did not correlate with reaction severity. Severe reactions tended to be either hypotensive (n = 19) or hypoxemic (n = 12). Levels of IL-6, IL-10, TNF receptor I, MCT, and histamine correlated with hypotension. No mediator correlated with hypoxemia or other respiratory features.

Conclusion: This study confirms that the concentrations of a number of cytokines are elevated in blood during anaphylaxis in human beings and that some correlate with the presence of hypotension. Others were only marginally elevated within a concentration range that available assays do not reliably detect. During respiratory reactions, mediators may be largely confined to the airways so that blood concentrations do not reflect activity.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Anaphylaxis / blood*
  • Anaphylaxis / immunology*
  • Cytokines / blood*
  • Female
  • Histamine / blood
  • Humans
  • Hypotension / blood
  • Hypotension / immunology
  • Male
  • Middle Aged
  • Prospective Studies
  • Tryptases / blood


  • Cytokines
  • Histamine
  • Tryptases