Splenic nerve
denervation abrogates enhanced splenic
cytokine gene expression responses to acute heating, demonstrating that
hyperthermia-induced activation of splenic sympathetic nerve discharge (SND) increases splenic
cytokine gene expression.
Hypothermia alters SND responses; however, the role of the sympathetic nervous system in mediating splenic
cytokine gene expression responses to
hypothermia is not known. The purpose of the present study was to determine the effect of
hypothermia on the relationship between the sympathetic nervous system and splenic
cytokine gene expression in anesthetized F344 rats. Gene expression analysis was performed using a microarray containing 112 genes, representing inflammatory
cytokines,
chemokines,
cytokine/
chemokine receptors and housekeeping genes. A subset of differentially expressed genes was verified by real-time RT-PCR analysis. Splenic SND was decreased significantly during cooling (core temperature decreased from 38 to 30 degrees C) in splenic-intact rats but remained unchanged in
sham-cooled splenic-intact rats (core temperature maintained at 38 degrees C).
Hypothermia upregulated the transcripts of several genes, including,
chemokine ligands CCL2, CXCL2, CXCL10, and CCL20, and
interleukins IL-1alpha, IL-1beta, and
IL-6. Gene expression responses to
hypothermia were similar for the majority of
cytokine genes in splenic-intact and splenic-denervated rats. These results suggest that
hypothermia-enhanced splenic
cytokine gene expression is independent of splenic SND.