The Effect of Pentoxifylline on IL-1beta and TNF-alpha mRNA Gene Expression in Hypoxic-Ischemic Brain Injury of Immature Rat

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.

Role of Inappropriate Antidiuretic Hormone Secretion in Hyponatremia associated with Febrile Convulsions

PURPOSE: Febrile convulsion is a common clinical problem in young children. In spite of their frequent occurrence, there is little information available about the value of investigation with febrile convulsion. Recent studies found a correlation between low serum sodium levels and risk of febrile convulsions. We carried out a study to evaluate the role of inappropriate ADH secretion in hyponatremia in relation to febrile convulsions. METHODS: This study used seventy cases(46 boys, 24 girls) with febrile convulsion, that were treated at the pediatric department of Korea University Medical Center Ansan hospital from Jan. 1998 to Aug. 1999. During the same period, thirty one cases(19 boys, 12 girls) with fever but without convulsion(control group I) and twenty four cases(16 boys, 8 girls) with convulsion but without fever(control group II) were evaluated in comparison with febrile convulsion group. Serum sodium, osmolality, vasopressin and urine osmolality of each group were measured on admission and analyzed by ANOVA. RESULTS: The mean serum sodium concentration of febrile convulsion group, control group I and control group II were 134.3+/-2.4mmol/L, 136.4+/-2.0mmol/L, and 136.0+/-2.2 mmol/L respectively. The serum sodium level of patient group was significantly lower than those of control group I and II(P<0.05). The case of the serum levels less than 135mmol/L was 54.3%(38/70) in patient group, 16.1%(5/31) in control group I and 12.5% (3/24) in control group II. Serum osmolality, uine osmolality of patients group were not significantly different from those of each control group. Vasopressin level of febrile convulsion group was higher than that of each control group. The risk of recurrent convulsion approaches 60%(15/25) of cases with hyponatremia less than 135mmol/L. CONCLUSION: We conclude that febrile convulsions are not mediated by hyponatremia but induce the changes in serum vasopressin and sodium level.