Hyperthermia-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system.
Whole body hyperthermia (WBH) has been used in experimental settings as an adjunct to radiochemotherapy for the treatment of various malignant diseases. The therapeutic effect of WBH has been hypothesized to involve activation of the immune system, although the effect of hyperthermia-induced activation of sympathetic nerve discharge (SND) on splenic immune function is not known. We tested the hypothesis that heating-induced splenic sympathoexcitation would alter splenic cytokine gene expression as determined using gene array and real-time RT-PCR analyses. Experiments were performed in splenic-intact and splenic-denervated anesthetized Sprague-Dawley rats (n=32). Splenic SND was increased during heating (internal temperature increased from 38 degrees to 41 degrees C) in splenic-intact rats but remained unchanged in nonheated splenic-intact rats. Splenic interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and growth-regulated oncogene 1 (GRO 1) mRNA expression was higher in heated than in nonheated splenic-intact rats. Splenic IL-1beta, IL-6, and GRO 1 mRNA expression was reduced in heated splenic-denervated compared with heated splenic-intact rats, but did not differ between heated splenic-denervated and nonheated splenic-intact rats. These results support the hypothesis that hyperthermia-induced activation of splenic SND enhances splenic cytokine gene expression.
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506, USA.
Chanran K
CK
Ganta
Frank
F
Blecha
Roman R
RR
Ganta
Bryan G
BG
Helwig
Sujatha
S
Parimi
Ning
N
Lu
Richard J
RJ
Fels
Timothy I
TI
Musch
Michael J
MJ
Kenney
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003199:Computer Systems; D016207:Cytokines / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D006979:Hyperthermia, Induced / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013154:Spleen / Q000098:blood supply / Q000737:chemistry* / Q000294:innervation / Q000378:metabolism*; D013562:Sympathectomy / Q000379:methods; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D016207:Cytokines