- Email: [email protected]
Friend or Foe? Linkage Between Hormonal Response and Innate Immunity
Journal of Surgical Research 172, 83–84 (2012) doi:10.1016/j.jss.2010.12.032
COMMENTARY Friend or Foe? Linkage Between Hormonal Response and Innate Immunity Originally submitted December 21, 2010; accepted for publication December 22, 2010
Development of various life support instruments has prolonged the survival times of severely injured or critically ill patients in the ICU. New, stronger antimicrobial agents with wider spectra provide opportunities to control severe infections. Nevertheless, the morbidity and mortality of these patients remain very high. We now recognize that understanding host response to surgical insults is essential for saving our patients. Indeed, during the past several decades, mechanisms underlying injury-induced organ dysfunction and immune-deficiency have been dramatically unveiled. However, the more intensive and extensive the research becomes, the more we recognize the complicated and profound interactions among host immunity, the neuro-endocrine system, metabolism, and the cardiovascular system. In a recent article published in the Journal of Surgical Research, Du and colleagues described the influences of major stress hormones on the responses of macrophages [1]. Preculture of rat peritoneal macrophages with corticosterone or epinephrine reduced Pam3CSK4- or lipopolysaccharideinduced TNFa production through down-regulation of toll like receptor expression. This report certainly gives us more information on the linkage between hormonal responses and innate immunity. Because the authors conducted an in vitro study, it is unclear whether down-regulation of innate immunity due to stress hormones results in a better or a worse outcome. Down-regulation of excessive production of TNFa at the local site, i.e., the peritoneal cavity, may prevent over-spill of TNFa into the systemic circulation, thereby inhibiting inflammation-related tissue injury [2]. Otherwise, a blunted peritoneal macrophage response may allow contaminating bacteria to develop into an abdominal abscess or further to disseminate to the systemic circulation [3]. It may be true that this crosstalk between innate immunity and the hormonal system provided a powerful means of surviving various insults before the dawn of modern medicine. It is also possible that this crosstalk may at times put patients in a more dangerous situation in the era of modern medicine. Although the authors found that high doses of stress hormones affect macrophage responses, it is unclear whether each hormone exists at the local site in such high doses. Future study is warranted to answer these questions. We still do not know the exact level to which innate immunity should be modulated under stressful conditions. Yet, we do now recognize that treating patients with awareness of the complex interactions between innate immunity and stress hormones may contribute to better outcomes.
83
0022-4804/$36.00 Ó 2012 Elsevier Inc. All rights reserved.
84
JOURNAL OF SURGICAL RESEARCH: VOL. 172, NO. 1, JANUARY 2012
Kazuhiko Fukatsu, M.D. Surgical Center The University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan E-mail: [email protected].
REFERENCES 1. Du Q, Min S, Chen LY, et al. Major stress hormones suppress the response of macrophages through down-regulation of TLR2 and TLR4. J Surg Res 2010, in press. 2. Cavaillon JM, Annane D. Compartmentalization of the inflammatory response in sepsis and SIRS. J Endotoxin Res 2006;12:151. 3. Lin MT, Saito H, Fukushima R, et al. Route of nutritional supply influences local, systemic, and remote organ responses to intraperitoneal bacterial challenge. Ann Surg 1996;223:84.
COMMENTARY Friend or Foe? Linkage Between Hormonal Response and Innate Immunity Originally submitted December 21, 2010; accepted for publication December 22, 2010
Development of various life support instruments has prolonged the survival times of severely injured or critically ill patients in the ICU. New, stronger antimicrobial agents with wider spectra provide opportunities to control severe infections. Nevertheless, the morbidity and mortality of these patients remain very high. We now recognize that understanding host response to surgical insults is essential for saving our patients. Indeed, during the past several decades, mechanisms underlying injury-induced organ dysfunction and immune-deficiency have been dramatically unveiled. However, the more intensive and extensive the research becomes, the more we recognize the complicated and profound interactions among host immunity, the neuro-endocrine system, metabolism, and the cardiovascular system. In a recent article published in the Journal of Surgical Research, Du and colleagues described the influences of major stress hormones on the responses of macrophages [1]. Preculture of rat peritoneal macrophages with corticosterone or epinephrine reduced Pam3CSK4- or lipopolysaccharideinduced TNFa production through down-regulation of toll like receptor expression. This report certainly gives us more information on the linkage between hormonal responses and innate immunity. Because the authors conducted an in vitro study, it is unclear whether down-regulation of innate immunity due to stress hormones results in a better or a worse outcome. Down-regulation of excessive production of TNFa at the local site, i.e., the peritoneal cavity, may prevent over-spill of TNFa into the systemic circulation, thereby inhibiting inflammation-related tissue injury [2]. Otherwise, a blunted peritoneal macrophage response may allow contaminating bacteria to develop into an abdominal abscess or further to disseminate to the systemic circulation [3]. It may be true that this crosstalk between innate immunity and the hormonal system provided a powerful means of surviving various insults before the dawn of modern medicine. It is also possible that this crosstalk may at times put patients in a more dangerous situation in the era of modern medicine. Although the authors found that high doses of stress hormones affect macrophage responses, it is unclear whether each hormone exists at the local site in such high doses. Future study is warranted to answer these questions. We still do not know the exact level to which innate immunity should be modulated under stressful conditions. Yet, we do now recognize that treating patients with awareness of the complex interactions between innate immunity and stress hormones may contribute to better outcomes.
83
0022-4804/$36.00 Ó 2012 Elsevier Inc. All rights reserved.
84
JOURNAL OF SURGICAL RESEARCH: VOL. 172, NO. 1, JANUARY 2012
Kazuhiko Fukatsu, M.D. Surgical Center The University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan E-mail: [email protected].
REFERENCES 1. Du Q, Min S, Chen LY, et al. Major stress hormones suppress the response of macrophages through down-regulation of TLR2 and TLR4. J Surg Res 2010, in press. 2. Cavaillon JM, Annane D. Compartmentalization of the inflammatory response in sepsis and SIRS. J Endotoxin Res 2006;12:151. 3. Lin MT, Saito H, Fukushima R, et al. Route of nutritional supply influences local, systemic, and remote organ responses to intraperitoneal bacterial challenge. Ann Surg 1996;223:84.