Postoperative Immune Suppression in Visceral Surgery: Characterisation of an Intestinal Mouse Model

Abstract

Background: Postoperatively acquired immune dysfunction is associated with a higher mortality rate in case of septic complications. As details of this severe clinical problem are still unknown, animal models are essential to characterise the mechanisms involved. Methods: Mice were laparotomised and the small intestine was pressed smoothly in antegrade direction. For extension of trauma, the intestine was manipulated three times consecutively. Following this, the ex vivo cytokine release of splenocytes was determined. The degree of surgical trauma was analysed by detection of HMGB1 and IL-6 in serum and by neutrophil staining in the muscularis mucosae. Results: We adapted the previously described animal model of intestinal manipulation to provide a model of surgically induced immune dysfunction. Following intestinal manipulation, the mice showed elevated serum levels of HMGB1 and IL-6 and increased infiltration of granulocytes into the muscularis mucosae. Ex vivo cytokine release by splenocytes was suppressed in the postoperative period. The degree of suppression correlated with the extent of surgical trauma. Conclusions: In this study, we describe a surgically induced immune dysfunction animal model, in which a significant surgical trauma is followed by an immune dysfunction. This model may be ideal for the characterisation of the postoperative immune dysfunction syndrome.

Surgical Trauma and Postoperative Immune Dysfunction

“…The influence of this surgical procedure on the immune status is described by the analysis of cytokine levels in serum and ex vivo cytokine release of splenocytes [21]. The immune status is additionally characterised by a significantly decreased white blood cell count 3 days following surgery when compared to mice that were laparotomised without touching the intestine.…”

“…Permission was obtained from the governmental committee on animal welfare (LALLF M-VL/TSD/7221.3-1.1-037/07). As described before [21], we laparotomised female C57BL/6 mice aged 8–12 weeks with an average body weight of 22 g. The small intestine was pressed smoothly between two sterile Q-tips, three times consecutively. In the laparotomy group, the abdomen was laid open and closed after several minutes without touching the intestine.…”

“…Our previously described model of surgically induced immune dysfunction (SID) is based on the intestinal trauma of an abdominal surgery procedure [20]. The intestine of mice is pressed smoothly, three times consecutively to induce a significant immune suppression as detected by the impaired ex vivo cytokine release of splenocytes [21]. Similar observations of trauma-induced immune suppression were made in mice with burn wounds: the concentration of peripheral blood leucocytes declined several hours following the trauma [22].…”

Surgical Trauma Leads to a Shorter Survival in a Murine Orthotopic Pancreatic Cancer Model

“…On days 11 and 21 following tumour implantation in mice, the intestine was manipulated as described before [16]. The small intestine was pressed smoothly in an antegrade direction between two sterile cotton wool swabs three times consecutively.…”

“…Second, orthotopic tumour growth is critical for the tumour microenvironment [13,14]. To investigate the influence of the postoperative immune dysfunction on tumour growth and tumour development, we combined an animal model of surgically induced immune dysfunction (SID) with a pancreatic carcinoma mouse model [15,16]. We analysed survival rates and studied the tumour development employing a 7-tesla MRI.…”