Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine Levels

• Published in: PloS one Vol. 10; no. 12; p. e0145635
• Main Authors: Bigler, Marc B, Egli, Simon B, Hysek, Cédric M, Hoenger, Gideon, Schmied, Laurent, Baldin, Fabian S, Marquardsen, Florian A, Recher, Mike, Liechti, Matthias E, Hess, Christoph, Berger, Christoph T
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.12.2015; Public Library of Science (PLoS)
• Subjects: Biocompatibility; CD18 antigen; Cell adhesion & migration; Cells, Cultured; Cellular stress response; Cross-Over Studies; CX3CR1 protein; Cytotoxicity; Detachment; Dopamine; Dosage and administration; Double-Blind Method; Drug abuse; Drug dosages; Drugs; Ecstasy (Drug); Epinephrine; Epinephrine - blood; Female; Flow Cytometry; Hormones; Humans; Immune system; Immunology; Immunophenotyping; Immunosuppressive agents; In vivo methods and tests; Innate immunity; Integrins; Internal medicine; Killer cells; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; L-selectin; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Male; MDMA; Medicine; Methylphenidate; Natural killer cells; NKG2 antigen; Peripheral blood; Peripheral circulation; Psychotropic drugs; Real-Time Polymerase Chain Reaction; Receptors; Receptors, Adrenergic, beta-2 - genetics; Receptors, Adrenergic, beta-2 - metabolism; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Stress response; Stress, Physiological - immunology; Stresses; Studies; Toxicity; Switzerland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0145635

Acute stress drives a 'high-alert' response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans. 3,4-methylenedioxymethamphetamine (MDMA), methylphenidate (MPH), or both, were administered to healthy volunteers in a randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset frequencies, natural killer (NK) cell immune-phenotypes, and changes in effector function were assessed, and linked to stress hormone levels and expression of CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells. MDMA/MPH > MDMA > MPH robustly induced an epinephrine-dominant stress response. Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, but they expressed slightly reduced levels of the activating receptor NKG2D. Preferential circulation of mature NK cells was associated with high epinephrine receptor expression among this subset, as well as expression of integrin ligands previously linked to epinephrine-induced endothelial detachment. The acute epinephrine-induced stress response was characterized by rapid accumulation of mature and functional NK cells in the peripheral circulation. This is in line with studies using other acute stressors and supports the role of the acute stress response in rapidly mobilizing the innate immune system to counteract incoming threats.