CALL FOR PAPERS Integrative and Translational Physiology: Inflammation and Immunity in Organ System Physiology Increased cytokine and chemokine gene expression in the CNS of mice during heat stroke recovery

Biedenkapp JC, Leon LR. Increased cytokine and chemokine gene expression in the CNS of mice during heat stroke recovery. Am J Physiol Regul Integr Comp Physiol 305: R978–R986, 2013. First published September 11, 2013; doi:10.1152/ajpregu.00011.2013.— Heat stroke (HS) is characterized by a systemic inflammatory response syndrome (SIRS) consisting of profound core temperature (Tc) changes in mice. Encephalopathy is common at HS collapse, but inflammatory changes occurring in the brain during the SIRS remain unidentified. We determined the association between inflammatory gene expression changes in the brain with Tc disturbances during HS recovery in mice. Gene expression changes of heat shock protein (HSP)72, heme oxygenase (hmox1), cytokines (IL-1 , IL-6, TNF), cyclooxygenase enzymes (COX-1, COX-2), chemokines (MCP-1, MIP-1 , MIP-1 , CX3CR1), and glia activation markers (CD14, aif1, vimentin) were examined in the hypothalamus (HY) and hippocampus (HC) of control (Tc 36.0°C) and HS mice at Tc,Max (42.7°C), hypothermia depth (HD; 29.3 0.4°C), and fever (37.8 0.3°C). HSP72 (HY HC) and IL-1 (HY only) were the only genes that showed increased expression at Tc,Max. HSP72 (HY HC), hmox1 (HY HC), cytokine (HY HC), and chemokine (HY HC) expression was highest at HD and similar to controls during fever. COX-1 expression was unaffected by HS, whereas HD was associated with approximately threefold increase in COX-2 expression (HY only). COX-2 expression was not increased during fever and indomethacin (COX inhibitor) had no effect on this Tc response indicating fever is regulated by other inflammatory pathways. CD14, aif1, and vimentin activation at HD coincided with maximal cytokine and chemokine expression suggesting glia cells are a possible source of brain cytokines and chemokines during HS recovery. The inflammatory gene expression changes during HS recovery suggest cytokines and/or chemokines may be initiating development or rewarming from hypothermia, whereas fever pathway(s) remain to be elucidated.