Matt Harmon

Chapter four 76 Abstract Objective The pathophysiology of hypothermia during sepsis is unclear. Using genomic profiling of blood leukocytes, we aimed to determine if hypothermia is associated with a different gene expression profile compared to fever during sepsis. Design Prospective observational study. Setting Two ICUs in tertiary hospitals in the Netherlands. Patients Patients with sepsis and either hypothermia or fever within 24 hours after ICU admission were included in the study (n = 168). Hypothermia was defined as body temperature below 36 °C. Fever was defined as body temperature equal to or above 38.3°C. Interventions Not applicable. Measurements and Main results We compared blood gene expression (whole- genome transcriptome in leukocytes) in hypothermic septic compared to febrile septic patients in an unmatched analysis and matched for APACHE IV score and the presence of shock. In total 67 septic patients were hypothermic and 101 patients were febrile. Hypothermia was associated with a distinct gene expression profile in both unmatched and matched analyses. There were significant differences related to the up- and downregulation of canonical signaling pathways. In the matched analysis the top upregulated gene was Cold-inducible mRNA binding protein (CIRBP) which plays a role in cold-induced suppression of cell proliferation. In addition, we found three signaling pathways significantly upregulated in hypothermic patients compared to febrile patients; tryptophan degradation X, phenylalanine degradation IV and putrescine degradation III. Conclusions There are distinct signaling pathways and genes associated with hypothermia, including tryptophan degradation and CIRBP expression , providing a possible link to the modulation of body temperature and immunosuppression. Future studies may focus on the canonical signaling pathways presented in this paper to further investigate spontaneous hypothermia in sepsis.