The small heat shock protein HSPB1 protects mice from sepsis.

In vitro studies have implicated the small heat shock protein HSPB1 in a range of physiological functions. However, its in vivo relevance is unclear as the phenotype of unstressed HSPB1 mice is unremarkable. To determine the impact of HSPB1 in injury, HSPB1 and wild type (WT) mice were subjected to cecal ligation and puncture, a model of polymicrobial sepsis. Ten-day mortality was significantly higher in HSPB1 mice following the onset of sepsis (65% vs. 35%). Ex vivo mechanical testing revealed that common carotid arteries from HSPB1 mice were more compliant than those in WT mice over pressures of 50-120 mm Hg. Septic HSPB1 mice also had increased peritoneal levels of IFN-γ and decreased systemic levels of IL-6 and KC. There were no differences in frequency of either splenic CD4 or CD8 T cells, nor were there differences in apoptosis in either cell type. However, splenic CD4 T cells and CD8 T cells from HSPB1 mice produced significantly less TNF and IL-2 following ex vivo stimulation. Systemic and local bacterial burden was similar in HSPB1 and WT mice. Thus while HSPB1 mice are uncompromised under basal conditions, HSPB1 has a critical function in vivo in sepsis, potentially mediated through alterations in arterial compliance and the immune response.