Can short-term administration of dexamethasone abrogate radiation-induced acute cytokine gene response in lung and modify subsequent molecular responses?
OBJECTIVE
To investigate the effects of short-term administration of dexamethasone (DEX) on radiation-induced responses in the mouse lung, focusing on expression of pro-inflammatory cytokine and related genes.


METHODS
At indicated times after thoracic irradiation and/or drug treatment, mRNA expression levels of cytokines (mTNF-alpha, mIL-1 alpha, mIL-1 beta, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-gamma) and related genes in the lungs of C3H/HeN mice were measured by RNase protection assay.


RESULTS
Radiation-induced pro-inflammatory cytokine mRNA expression levels in lung peak at 6 h after thoracic irradiation. DEX (5 mg/kg) suppresses both basal cytokine mRNA levels and this early response when given immediately after irradiation. However, by 24 h, in mice treated with DEX alone or DEX plus radiation, there was a strong rebound effect that lasted up to 3 days. Modification of the early radiation-induced response by DEX did not change the second wave of cytokine gene expression in the lung that occurs at 1 to 2 weeks, suggesting that early cytokine gene induction might not determine subsequent molecular events. A single dose of DEX attenuated, but did not completely suppress, increases in cytokine mRNA levels induced by lipopolysaccharide (2.5 mg/kg) treatment, but, unlike with radiation, no significant rebound effect was seen. Five days of dexamethasone treatment in the pneumonitic phase also inhibited pro-inflammatory cytokine gene expression and, again, there was a rebound effect after withdrawal of the drug.


CONCLUSIONS
Our findings suggest that short-term use of dexamethasone can temporarily suppress radiation-induced pro-inflammatory cytokine gene expression, but there may be a rebound after drug withdrawal and the drug does little to change the essence and course of the pneumonitic process.
Hong
J H
JH
Department of Radiation Oncology, Chang Gung Memorial Hospital and School of Medicine, Chang Gung University, Tao-Yuan, Taiwan. jihong@adm.cgmh.org.tw
Chiang
C S
CS
Tsao
C Y
CY
Lin
P Y
PY
Wu
C J
CJ
McBride
W H
WH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D007378:Interleukins / Q000378:metabolism* / Q000528:radiation effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects
D000893:Anti-Inflammatory Agents; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone