Surgical stress reduces mortality from endotoxin shock.
OBJECTIVE
Surgical stress has been considered a preliminary to multiple organ failure through what has been termed a "two-hit" mechanism. Recent evidence, however, suggests that such stress has a beneficial influence in reducing endotoxin [lipopolysaccharide (LPS)]-mediated lethality. This study has been an effort to clarify whether and how LPS-mediated septic shock is prevented by a previous insult with mild (laparotomy) or severe (hepatectomy) surgical stress.


METHODS
LPS was injected intraperitoneally into mice after two-thirds hepatectomy or laparotomy only. Survival rates, and protein and messenger RNA (mRNA) levels for tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured.


RESULTS
Most of the unoperated control mice died within 3 days after the LPS challenge. Mortality following LPS injection was reduced after laparotomy only or hepatectomy (P<0.05). A significant reduction in the mortality was observed from 2 days to 7 days after laparotomy only, and from 2 days to 4 weeks after hepatectomy. Correspondingly, the increase in the serum levels of TNF-alpha and IL-6 induced by the LPS injection was partially impaired by either laparotomy only or hepatectomy at an early (2 days) postoperative stage (P<0.05). At a later (7 days) stage, however, the serum level of IL-6 and its mRNA level in the spleen were elevated after the LPS challenge more quickly in the hepatectomy group than in the unoperated control group ( P<0.05).


CONCLUSIONS
Surgical stress reduces LPS-induced lethality through biphasically regulating the levels of TNF-alpha and IL-6 production.
Kamei
Keitarou
K
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Nimura
Yuji
Y
Nagino
Masato
M
Aono
Keiya
K
Nakashima
Izumi
I
D000199:Actins / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D006498:Hepatectomy / Q000009:adverse effects*; D015850:Interleukin-6 / Q000097:blood; D007813:Laparotomy / Q000009:adverse effects*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism* / Q000401:mortality*; D013312:Stress, Physiological / Q000209:etiology* / Q000378:metabolism*; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000199:Actins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha