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.