| The Effect of Pentoxifylline on IL-1beta and TNF-alpha mRNA Gene Expression in Hypoxic-Ischemic Brain Injury of Immature Rat. |
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Kyoung Burm Kim, Gi Hyun Jeon, Young Rae Kim, Jung Hwa Lee, Kee Hyoung Lee, Baik Lin Eun, Soon Kyum Kim |
1Department of Pediatrics, College of Medicine and School of Medicine, Korea University, Korea.
2Department of Pediatrics, Pochon CHA University, Seoul, Korea. |
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| Abstract |
PURPOSE
Interleukin-1beta(IL-1beta) and Tumor necrosis factor-alpha(TNF-alpha) are multifunctional cytokines that may play important roles both in the normal development of central nervous system and in the response of brain to diverse forms of injury. IL-1beta and TNF-alpha have potent proinflammatory action and the potential to modulate cell growth. Cerebral hypoxia-ischemia selectively stimulates IL-1beta and TNF-alpha gene expression in brain regions susceptible to irreversible injury in perinatal rats. Pentoxifylline, a cAMP phosphodiesterase inhibitor, attenuates hypoxic-ischemic brain injury in immature rats and inhibits TNF-alpha expression at the transcription level. We hypothesize that pentoxifylline would attenuate the expression of IL-1beta and TNF-alpha mRNA gene expression on hypoxic-ischemic brain injury in immature rats. METHODS: To elicit focal hypoxic-ischemic brain injury, 7-d-old(P7) rats underwent right carotid artery ligation, followed by 3 hr of hypoxia(fractional concentration of inspired O2=0.08). In 3 rats, pentoxifylline(40mg/kg) was injected into the intraperitoneal cavity immediately before and after hypoxia. The other 4 rats were given PBS solutions. IL-1beta and TNF-alpha mRNA content were measured by reverse transcription followed by polymerase chain reaction amplification(RT-PCR) in the samples prepared from the lesioned and contralateral hemispheres killed 4 hr post-hypoxia. cDNA were amplified with primers specific for IL-1beta and TNF-alpha. and also amplified with GAPDH primers which served as an internal control. RESULTS: In control group, hypoxia-ischemia induced IL-1beta and TNF-alpha mRNA expression from the lesioned hemisphere in immature rat brain. In pentoxifylline treated group, IL-1beta and TNF-alpha mRNA expression were attenuated at 4 hr post hypoxia- ischemia. CONCLUSION: Preteatment with pentoxifylline decreased incidence and severity of hypoxic-ischemic injury in immature rat brain. Pentoxifylline attenuated the expression of IL-1beta and TNF-alpha gene on hypoxic-ischemic injury in immature rat brain. IL-1beta and TNF-alpha may play important roles in the response of the developing brain to acute hypoxic-ischemic injury. |
| Key Words:
IL-1beta, TNF-alpha, Pentoxifylline, Hypoxia-ischemia, Immature brain |
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