HMGB1 mediates splenomegaly and expansion of splenic CD11b+ Ly-6Chigh inflammatory monocytes in murine sepsis survivors.

Valdés-Ferrer SI, Rosas-Ballina M, Olofsson PS, Lu B, Dancho ME, Ochani M, Li JH, Scheinerman JA, Katz DA, Levine YA, Hudson LK, Yang H, Pavlov VA, Roth J, Blanc L, Antoine DJ, Chavan SS, Andersson U, Diamond B, Tracey KJ.
Journal   J Intern Med.
Species  
Analytes Measured   IL-10 , IL-12 p70 , IL-6
Matrix Tested   Plasma
Year   2013
Volume  
Page Numbers  
Application   Cytokines and Chemokines
Abstract
More than 500,000 hospitalized patients survive severe sepsis annually in the USA. Recent epidemiological evidence, however, demonstrated that these survivors have significant morbidity and mortality, with 3-year fatality rates higher than 70%. To study this 'severe sepsis survivor syndrome', we recently described an animal model of murine peritonitis, in which surviving animals were monitored for several months after recovery from acute perforated bowel and infection. Unexpectedly, in the present study, we observed that apparently normal animals developed significant splenomegaly following severe sepsis. Analysis of the principal splenic cellular compartments revealed a major expansion of the inflammatory CD11b+ Ly-6Chigh pool. Serum high mobility group box 1 (HMGB1) levels in the mice that survived sepsis were significantly elevated for 4 to 6 weeks after the acute infection, and administration of an anti-HMGB1 monoclonal antibody significantly reversed splenomegaly. Administration of recombinant HMGB1 to healthy mice mediated splenomegaly, indicating that prolonged elevation of HMGB1 is a necessary and sufficient mediator of splenomegaly and splenocyte expansion in severe sepsis survivors.

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