Patchen M L, MacVittie T J, Williams J L, Schwartz G N, Souza L M
Department of Experimental Hematology, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5145.
Blood. 1991 Feb 1;77(3):472-80.
Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies in our laboratory have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL-6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 (1,000 micrograms/kg) on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline-treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.
放疗后造血功能抑制以及随后对潜在致命性机会性感染的易感性是有充分文献记载的现象。治疗性减轻辐射诱导的骨髓抑制的方法可能具有巨大的临床价值。我们实验室的体内研究表明，白细胞介素-6（IL-6）可刺激正常小鼠的多能造血干细胞（CFU-s）、粒细胞-巨噬细胞祖细胞（GM-CFC）和红系祖细胞（CFU-e）增殖。基于这些结果，还评估了IL-6在辐射诱导的造血损伤后刺激造血再生的能力。将C3H/HeN雌性小鼠暴露于6.5 Gy的60Co辐射下，并在照射后第1至3天或第1至6天皮下注射生理盐水或IL-6（1000微克/千克）。在第7、10、14、17和22天，测定股骨和脾脏中的CFU-s、GM-CFC和CFU-e含量以及外周血白细胞、红细胞和血小板计数。与生理盐水治疗相比，3天和6天的IL-6治疗均加速了造血恢复；6天治疗效果更佳。例如，与正常对照值（N）相比，照射后17天接受IL-6治疗的小鼠股骨和脾脏中的CFU-s数量分别为27%N和136%N，而生理盐水治疗的小鼠分别为2%N和10%N。同时，骨髓和脾脏中的GM-CFC值分别为58%N和473%N，而生理盐水治疗的小鼠分别为6%N和196%N；骨髓和脾脏中的CFU-e数量分别为91%N和250%N，而生理盐水治疗的小鼠分别为31%N和130%N；外周血白细胞、红细胞和血小板值分别为210%N、60%N和24%N，而生理盐水治疗的小鼠分别为18%N、39%N和7%N。这些研究表明，治疗性给予IL-6可有效加速辐射诱导的造血损伤后的多谱系造血恢复。
