Lactate in Anaphylaxis: 100 Years On.

Lactate is a ubiquitous and pleiotropic signalling molecule, with important functional effects in tissue and cellular metabolism. As an exerkine, lactate is not only substantially released from tissues during exercise but may also play a role in exercise-related medical conditions. Since exercise is a known co-factor in anaphylaxis, this may suggest a mechanistic relevance for lactate release during anaphylactic events. Here, we evaluated in vitro and in vivo evidence for lactate release from mast cells (MCs) from preclinical microdialysis studies, animal models and clinical data in anaphylaxis. Lactate levels are markedly elevated in both animal models of anaphylaxis and patients with anaphylaxis. Although not causative, lactate is clearly relevant to many different steps in anaphylaxis, including MC activation, vascular permeability and gastrointestinal dysfunction, but currently lacks a comprehensive interpretation framework in anaphylaxis. As a result, lactate cannot be currently considered a biomarker of anaphylaxis per se. However, given its wide dynamic range, a plethora of available lactate biosensors, and the ease of measurement in various biological fluids, lactate may be a potential candidate for biomarker development. At present, lactate's contribution to anaphylaxis, which was discovered a century ago by Zunz and La Barre, has not been fully elucidated. Unresolved issues in anaphylaxis include the patient's metabolic state; the kinetics of lactate release and its biological actions; MC bioenergetics and metabolome; activation thresholds; and feedback mechanisms, as well as an expression of lactate-metabolizing enzymes. A closer focus on these known unknowns may demystify the contribution of lactate in anaphylaxis and beyond.