Social stress desensitizes lymphocytes to regulation by endogenous glucocorticoids: insights from in vivo cell trafficking dynamics in rhesus macaques.
OBJECTIVE
To determine whether chronic social stress can desensitize leukocytes to normal physiologic regulation by endogenous glucocorticoids.


METHODS
We analyzed the longitudinal relationship between plasma cortisol levels and peripheral blood lymphocyte counts over 16 monthly assessments in 18 rhesus macaques randomized to recurrent social encounters with a stable set of conspecifics or continually varying social partners (unstable socialization).


RESULTS
Animals socialized under stable conditions showed the expected inverse relationship between plasma cortisol concentrations and circulating lymphocyte frequencies. That relationship was significantly attenuated in animals subject to unstable social conditions. Differences in leukocyte redistributional sensitivity to endogenous glucocorticoids emerged within the first week of differential socialization, persisted throughout the 60-week study period, and were correlated with other measures of glucocorticoid desensitization (blunted hypothalamic-pituitary-adrenal (HPA) axis response to acute stress and redistributional response to dexamethasone challenge). Effects of unstable social conditions on leukocyte sensitivity to cortisol regulation were not related to physical aggression.


CONCLUSIONS
Chronic social stress can impair normal physiologic regulation of leukocyte function by the HPA axis in ways that may contribute to the increased physical health risks associated with social adversity.
Cole
Steve W
SW
Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, 11-934 Factor Building, Los Angeles, California 90095-1678, USA. coles@ucla.edu
Mendoza
Sally P
SP
Capitanio
John P
JP
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000097:blood / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D012919:Social Behavior; D013315:Stress, Psychological / Q000097:blood* / Q000276:immunology
D005938:Glucocorticoids; D003907:Dexamethasone; D006854:Hydrocortisone