Gough D B, Moss N M, Jordan A, Grbic J T, Rodrick M L, Mannick J A
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Surgery. 1988 Aug;104(2):292-300.
Impaired immune competence leading to decreased resistance to sepsis is a major cause of death in burn patients. We have previously shown that increased mortality from a septic challenge correlated with impaired splenocyte interleukin-2 (IL-2) production and response to T cell mitogens in mice subjected to a 25% surface area scald burn. We report now that the addition of recombinant (r) IL-2 (100 U/ml) in vitro to splenocytes from burned animals restored mitogen responses to normal. Burned mice intraperitoneally received 16,000 U of rIL-2 (selected on the basis of dose-response experiments) once daily in 0.5 ml 5% dextrose (5% D) on days 1 through 6 after thermal injury and were compared with burned mice treated with only 5% D. Both groups were subjected to cecal ligation and puncture 10 days after burn; 4 days later, there were no survivors in the 5% D group, whereas 45% of the rIL-2 group remained alive (p = 0.001; Gehan statistic). We found that rIL-2 treatment at the dose selected resulted in no apparent toxicity in burned mice. Finally, splenocytes from rIL-2-treated burned mice showed improved responses to T cell mitogens in vitro compared with 5% D-treated controls. We conclude that rIL-2 therapy may have a role in the restoration of immune competence after thermal injury.
免疫能力受损导致对脓毒症的抵抗力下降是烧伤患者死亡的主要原因。我们之前已经表明，在遭受25%体表面积烫伤的小鼠中，脓毒症激发导致的死亡率增加与脾细胞白细胞介素-2（IL-2）产生受损以及对T细胞有丝分裂原的反应有关。我们现在报告，在体外将重组（r）IL-2（100 U/ml）添加到烧伤动物的脾细胞中可使有丝分裂原反应恢复正常。热损伤后第1至6天，烧伤小鼠每天腹腔注射16,000 U的rIL-2（根据剂量反应实验选择），溶于0.5 ml 5%葡萄糖（5% D）中，并与仅用5% D治疗的烧伤小鼠进行比较。两组在烧伤后10天进行盲肠结扎和穿刺；4天后，5% D组无存活者，而rIL-2组45%仍存活（p = 0.001；Gehan统计量）。我们发现，所选剂量的rIL-2治疗在烧伤小鼠中未产生明显毒性。最后，与5% D治疗的对照组相比，rIL-2治疗的烧伤小鼠的脾细胞在体外对T细胞有丝分裂原的反应有所改善。我们得出结论，rIL-2治疗可能在热损伤后免疫能力的恢复中发挥作用。
