Abstract # 1856 Breast cancer patients undergoing surgery and subjected to perioperative inhibition of COX-2 and β-adrenoceptor blockade: Effects on number and cytotoxicity of circulating NK cells and their relations to cytokine levels

Abstract

Preclinical research has implicated the release of catecholamines, glucocorticoids, and prostaglandins in mediating the effects of stress and surgery on NK cell cytotoxicity (NKCC) and distribution. Whereas ex-vivo findings regarding cell distribution are valid, we recently reported that the direct effects of catecholamines and prostaglandins on NKCC are transient and not reflected ex-vivo. Here, in a double-blind placebo-controlled randomized clinical trial in 36 breast cancer patients, we tested a combined perioperative β-adrenoceptor and COX-2 blockade, using propranolol and etodolac, respectively. An 11-day oral drug treatment was initiated five days prior to surgery. Blood samples were taken before treatment (T1), on the mornings before and after surgery (T2& T3), and after treatment cessation (T4). Cortisol levels were unaffected by treatment, increasing from T1 to T2, and progressively decreased at T3 and T4. Circulating NK cell numbers increased in placebo-treated patients preparing for surgery (T1–T2), while drug treatment significantly inversed this pattern, presumably through β -adrenergic blockade. Postoperatively (T3), a significant decrease in NK cell numbers, NKCC/ml, and NKCC/NK cell were evident in both groups, without correlation to serum cortisol levels. Interestingly, IL-6 and IL-10 serum levels were inversely related to NKCC/ml and NKCC/NK cell, but not to NK cell numbers, suggesting a minor role for NK cell numbers in perturbed T3 NKCC. These findings further demonstrate the complexity of ex-vivo assessment of NK cell parameters.