Impact of Buprenorphine Extended-Release (Ethiqa XR) on mice exposed to aerosolized Burkholderia pseudomallei and Yersinia pestis 2253137

Abstract Introduction Buprenorphine is a potent partial opioid used to manage pain and opioid dependence. The buprenorphine extended-release formulation, Ethiqa XR (Ethiqa), has been FDA-indexed for mice and other laboratory species to relieve pain, however, several reports indicate that Ethiqa can alter the inflammatory response in various in vivo models. Therefore, it is necessary to understand the effect of Ethiqa on disease pathogenesis prior to its use during animal studies. Methods Here, we evaluated the effects of Ethiqa treatment prior to and 48h after bacterial challenge of C57BL/6 and BALB/c mice with Burkholderia pseudomallei and Yersinia pestis. Results Both mouse strains challenged with aerosolized Burkholderia pseudomallei K96243 demonstrated increased bacterial dissemination to the spleen when treated with Ethiqa. Consistently, splenocytes had elevated pro-inflammatory cytokines such as IFN-gamma, IL-6, IL-22, TNF-alpha, among others, as well as elevated levels of iNOS. The C57BL/6 mice also displayed elevated IFN-gamma and IP-10/CXCL10 in lung and brain homogenates. In contrast, no profound differences were observed in either mouse strain treated with Ethiqa and challenged with Yersinia pestis CO92. In the absence of challenge, treatment with Ethiqa did not change the cytokine responses in the lung, brain, or spleen of BALB/c mice but increased the concentration of IL-6 and TNF-alpha in the lungs of C57BL/6 mice. Conclusion Taken together, these results suggest the effects of Ethiqa may be model-specific and introduce confounding effects that would impact dependent variables. Funding Source DTRA-JSTO Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)