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

Abstract

Anaphylaxis is generally unanticipated and requires emergency management. Therefore, the biological mediators in human beings have been difficult to define. Our aim was to identify cytokines and chemokines whose concentrations increase during anaphylaxis in human beings and to determine how each correlates with severity. 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. 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. 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.