Abstract
Tumor necrosis factor α (TNFα) is a pro-inflammatory cytokine that has a wide variety of bioactivities. TNFα plays a central role in immune system, but over-production of TNFα leads to inflammatory disorders. Recent reports have shown that anti-TNFα agents prevent radiation-induced damage. We used wild-type (TNFα+/+) and TNFα knockout (TNFα-/-) BALB/c mice to clarify the role of TNFα in high-dose radiation exposure. We studied the survival rate of TNFα+/+ and TNFα-/- mice that were exposed to whole body irradiation. Thirty days after irradiation with 6 Gy, the survival rates were 100% and 54% in TNFα+/+ and TNFα-/- mice, respectively. Thus, the survival durations in TNFα-/- mice were shorter than that in TNFα+/+ mice. Administration of recombinant TNFα improved the survival rate on day 30 to 100% in irradiated TNFα-/- mice. The numbers of RBC, Hb levels, and Ht values were significantly lower in TNFα-/- mice than those in TNFα+/+ mice on 15 days after irradiation. However, there was no significant difference in other hematological values between both groups. On the other hand, the level of serum iron in TNFα-/- mice was approximately twofold higher compared with that in TNFα+/+ mice, but there was no significant difference in other biochemical value such as liver function test between both groups. The histological analysis found no marked difference of injuries including hemorrhage between both mice. Our results suggest that endogenously produced TNFα may play important roles in erythropoiesis of irradiated mice. Further studies are in progress.
