71. Surprise, surprise: Glucocorticoids have a minor role compared to catecholamines and prostaglandins in mediating stress and surgery-induced In vivo suppression of NK activity

• Published in: Brain, behavior, and immunity Vol. 32; p. e21
• Main Authors: Ben-Eliyahu, S, Rosenne, E, Sorski, L, Shaashua, L, Neeman, E, Matzner, P, Levi, B, Gotlieb, N
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2013
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2013.07.083

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, these findings are insufficient to conclude regarding the impact of endogenous release of these factors on in vivo levels of NKCC. 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 this end we administered corticosterone, epinephrine, or prostaglandins to rats, or antagonized their endogenous release following different stress paradigms or surgery. The results indicated that corticosterone can modulate in vivo levels of NKCC 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 and/or prostaglandins; and (iv) was completely abolished through antagonizing epinephrine and/or 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 and/or prostaglandins as effective and clinically feasible approaches to overcome such NK immuno-suppressive effects.