Abstract
Anesthetics are known to modulate host immune responses, but separating the variables of surgery from anesthesia when analyzing hospital acquired infections is often difficult. Here, the bacterial pathogen Listeria monocytogenes (Lm) was used to assess the impact of the common anesthetic propofol on host susceptibility to infection. Brief sedation of mice with physiologically relevant concentrations of propofol increased bacterial burdens in target organs by more than 10,000-fold relative to infected control animals. The adverse effects of propofol sedation on immune clearance of Lm persisted after recovery from sedation, as animals given the drug remained susceptible to infection for days following anesthesia. In contrast to propofol, sedation with alternative anesthetics such as ketamine/xylazine or pentobarbital did not increase susceptibility to systemic Lm infection. Propofol altered systemic cytokine and chemokine expression during infection, and prevented effective bacterial clearance by inhibiting the recruitment and/or activity of immune effector cells at sites of infection. Propofol exposure induced a marked reduction in marginal zone macrophages in the spleens of Lm infected mice, resulting in bacterial dissemination into deep tissue. Propofol also significantly increased mouse kidney abscess formation following infection with the common nosocomial pathogen Staphylococcus aureus. Taken together, these data indicate that even brief exposure to propofol severely compromises host resistance to microbial infection for days after recovery from sedation.
Highlights
Microbial infection is a major complication for surgical patients in the US, occurring in the aftermath of ~2% of all surgeries [1]
Listeria monocytogenes (Lm) is a facultative intracellular bacterial pathogen that has been used for decades as a tool to elucidate host immune responses to bacterial infection via mouse infection models [16,17,18]
Control animals were given intravenous Intralipid carrier, and both groups were intravenously inoculated via the tail vein with a sub-lethal dose of 2 x 104 CFU of Lm mixed immediately prior to injection with either drug or Intralipid carrier
Summary
Microbial infection is a major complication for surgical patients in the US, occurring in the aftermath of ~2% of all surgeries [1]. Significant effort has been focused on reducing patient exposure to infectious agents at the time of surgery; recently attention has been directed to determine whether anesthetics impact patient susceptibility to infection. A recent in vivo study using a cecal ligation and puncture model of sepsis in rats has indicated that continuous exposure to propofol for 24 hours resulted in elevated mortality compared to rats exposed to inhalation anesthetic [10]. Samples were washed in TBS incubated with rabbit antiserum against Lm (BD Pharmingen, San Diego, CA) and rat anti-mouse SIGN-RI antibody against marginal zone macrophages in the spleen (AbD Serotec, Raleigh, NC), or rabbit anti-mouse CD3 antibody against T cells (Abcam, Cambridge, MA) for 1 hour at room temperature or overnight at 4°C. Slides were washed in TBS incubated sequentially with donkey anti-rabbit AF-488 or goat anti-rat AF-594 (Abcam, Cambridge, MA) for 1 hour at room temperature. Slides were imaged using the Zeiss Axio Imager A2 manual upright research microscope.
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