The Effect of Toll Like Receptor (Tlr) 9 Agonist, Cpg Oligodeoxynucleotides (Odn), On Abdominal and Gastrotomy Wound Healing in a Murine Model
Ik-Yong Kim*1,2, Xiaohong Yan1, Raymond Baxter1, Thomas R. Gardner3, Chandana Shantha Kumara Hm1, Aqeel Ahmed4, Carlos Cordon-Cardo4, Richard L. Whelan1
1Colorectal Surgery, Columbia University, New York, NY; 2Surgery, Yonsei University, Wonju College of Medicine, Wonju, South Korea; 3Orthopedic Surgery, Columbia University, New York, NY; 4Pathology, Columbia University, New York, NY
Introduction: The synthetic TLR9 ligand, CpG ODN (CpG) has been used clinically as an anti-cancer immunotherapy. It has largely been used in the adjuvant or stage 4 setting. It has been shown experimentally that CpG, when given alone prior to surgery (preop), limits postoperative tumor growth. Perioperative (Periop) CpG might also limit post-surgical immunosuppression. Prior to human periop studies CpG’s impact on wound healing must be determined. This study’s purpose was to assess abdominal wall wound and anastomotic healing after periop CpG.
Methods: Thirty Balb/C mice were randomized into 2 groups and given CpG 1826 (20 ug/dose) or PBS via i.p. both PreOP (7, 5, 3, and 1 day before surgery) and on PostOP day (POD) 1, 2, and 3. All mice underwent a laparotomy and gastrotomy that were carefully suture closed. The mice were sacrificed on POD7 and 21 and their abdominal pelts and stomachs excised. Tensometry was used to determine the peak force and total energy required to disrupt the abdominal wall wounds while the bursting pressure of the gastric wounds was measured via saline infusion. The Sircol assay was used to determine soluble collagen content and a blinded pathologist used a wound healing scoring system histologically to assess the pelts.
Results: There were no significant differences in the bursting pressures of the gastrotomy wounds or in the peak force or total energy needed to disrupt the abdominal wounds when comparing the results of treated group to those of the control group on POD7 or 21. In regards to abdominal wound collagen content, no differences were noted between the control and treated groups at either time point. Importantly, there were no abdominal wall dehiscence or clinical gastrotomy leaks in CpG treated group. The histologic healing assessment scores were similar between groups.
Conclusions: Perioperative administration of CpG doesn’t appear to have a negative impact on abdominal wall or gastric wound healing in mice. Although it is not possible to extrapolate these results directly to the human setting, these findings lend support to the concept of a human Phase I perioperative CpG study.
