title: In vivo suppression of NK cell cytotoxicity by stress and surgery: glucocorticoids have a minor role compared to catecholamines and prostaglandins.
abstract: Most in vitro and ex-vivo studies indicate a profound suppression of NK cell cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins were reported both to suppress and to enhance NKCC. However, methodological considerations hinder our ability to deduce from these findings to the impact of endogenous release of these factors on in vivo levels of NKCC and their implications to NK-dependent resistance to pathologies in living humans or animals. Here we used an in vivo approach that sensitively and specifically reflects NKCC in living F344 rats, based on lung clearance of NK-sensitive tumor cells (MADB106), and based on comparing effects between NK-intact and NK-depleted rats. To study the role of corticosterone, epinephrine, and prostaglandins, we administered these factors to rats, or antagonized their endogenous release following different stress paradigms or surgery. The results indicated that endogenous or exogenous elevated corticosterone levels can suppress in vivo NKCC levels, but only under some conditions, and mostly secondarily to the NK-suppressing impact of epinephrine. Specifically, corticosterone-induced NKCC suppression occurred (i) only under prolonged, but not short exposure to stress, and mainly in males; (ii) was smaller than the prominent impact of epinephrine; (iii) was mostly ascribed to corticosterone-induced potentiation of the effects of epinephrine or/and prostaglandins; and (iv) was completely abolished through antagonizing epinephrine or/and prostaglandins. Overall, these findings markedly limit the significance of stress/surgery-induced corticosterone release in the in vivo suppression of NKCC, and highlight the blockade of epinephrine or/and prostaglandins as effective and clinically feasible approaches to overcome such immuno-suppressive effects.
authors: Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
authors: Ella
authors: E
authors: Rosenne
authors: Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
authors: Liat
authors: L
authors: Sorski
authors: Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
authors: Lee
authors: L
authors: Shaashua
authors: Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
authors: Elad
authors: E
authors: Neeman
authors: Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
authors: Pini
authors: P
authors: Matzner
authors: Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel.
authors: Ben
authors: B
authors: Levi
authors: Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel. Electronic address: shamgar@post.tau.ac.il.
authors: Shamgar
authors: S
authors: Ben-Eliyahu
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D002395:Catecholamines / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D003345:Corticosterone / Q000493:pharmacokinetics / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary; D008297:Male; D011453:Prostaglandins / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D013312:Stress, Physiological
chemical_list: D002395:Catecholamines; D005938:Glucocorticoids; D011453:Prostaglandins; D003345:Corticosterone
keywords: Catecholamines; Glucocorticoids; In vivo; NK cell cytotoxicity; Prostaglandins