Intestinal Anastomosis Surgery with No Septic Shock Primes for a Dysregulatory Response to a Second Stimulus

Abstract

Major surgery is believed to contribute to immune dysregulation and high susceptibility to microbes. Recently, the inflammatory "two-hit" model has been accepted to elucidate development of multiple organ failure in surgical patients. Our purpose was to examine whether intestinal surgery, which causes a minor insult with no septic shock, may modify the immune response to exogenous LPS as a second stimulus. Using a rat intestinal transection and anastomosis surgery model, we sequentially examined blood cell counts, body temperatures, and plasma cytokines. Rats were administered with LPS intravenously or intratracheally various days after surgery. Phagocytic activity and TNFalpha production in bronchoalveolar lavage (BAL) cells, plasma cytokines, and survival rates were evaluated. The surgery itself caused no severe shock or circulating cytokine elevation, whereas the number of granulocytes in the blood was significantly elevated after surgery. LPS-induced elevation of circulating IFNgamma attenuated 3 days after surgery. In contrast, IL-10 was enhanced 3-10 days after surgery. Hyporesponsiveness of BAL cells to LPS was observed 3 days after surgery but not the next day after surgery. However, rats intratracheally exposed to LPS 10-13 days after surgery exhibited higher mortality. Although our surgical procedure was not supposed to be a severe insult, it sufficiently primed rats for an altered response to a second stimulus (endotoxin), which included enhanced mortality. This study provided an improved understanding of pathophysiological changes following surgery and described a useful model for developing preventive and therapeutic strategies for complications after surgery.