Increased extracellular heat shock protein 90 in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children

Mammalian heat-shock-protein (HSP) 90 rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90 is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90 relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90 and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90 compared to H (P<0.01). HSP90 was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P<0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P<0.05).Serum HSP90 is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90 is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern.