Abstract: TH-PO440

Latent CMV reinforces Myeloid Inflammation in the Kidney and Other Organs Following a Septic Episode

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Nash, William, University of Virginia, Charlottesville, Virginia, United States
  • Swaminathan, Sundararaman, University of Virginia, Charlottesville, Virginia, United States
  • Brown, Michael G, University of Virginia, Charlottesville, Virginia, United States
Background

Although CMV reactivation is a well-known complication of renal transplant, the impact of CMV infection outside of the transplant field is relatively understudied. Reactivation of latent viral infections is a common occurrence in ICU patients diagnosed with sepsis and this coincides with high frequency of kidney dysfunction and failure. To date, such viral reactivation has been mostly viewed as a symptom of lympho-depression that can occur alongside or following the hyperinflammatory stage of sepsis. However, recent studies have indicated that CMV reactivation during sepsis is associated with longer hospital stays and increased risk of death.

Methods

We are designing a two-hit model to investigate the impact of latent CMV infection on sepsis. Mice are infected with MCMV for 60+ days to establish a latent infection. Naïve mice are used as comparators. A sepsis-like state is then induced by intraperitoneal injection of a cecal slurry prepared from naïve mice. Mice are monitored for 15 days post-septic insult and then serum and tissues are analyzed.

Results

All mice lost weight following cecal slurry injection, but we observed greater fluctations in body weight during recovery from sepsis in CMV(+) mice. In addition, of the 6 CMV(+) mice, one developed a massively cystic kidney and another exhibited aberrantly high numbers of monocytes in the lung and kidney. Mice that were previously infected with CMV displayed a greater proportion of Ly6C-hi inflammatory monocytes in the kidney as well as in the spleen, liver, and lung. Kidney and lung tissue from CMV+ mice also had a greater concentration of neutrophils per gram of tissue. At the time point investigated, we did not detect differences in histology, serum creatinine, or serum BUN between CMV(+) and CMV(-) mice, but the cecal slurrly dose used was generally well tolerated since all mice survived.

Conclusion

Our study shows that CMV may reinforce the myeloid inflammation occuring during sepsis. The tissues of mice previously infected with CMV maintain an inflammatory-skewed environment out to 15 days post-septic insult, even when mice are recovering body weight. It will be interesting to know if this skew predisposes mice to increased pathology in the kidney and lung upon additional infection and to determine the effects of CMV during more severe septic episodes.

Funding

  • NIDDK Support