Tritarelli E, Greco G, Testa U, Belardelli F, Peschle C, Proietti E
Department of Virology, Istituto Superiore di Sanità, Rome, Italy.
Cancer Res. 1994 Dec 15;54(24):6469-76.
We have studied the effects of single and combined treatment with recombinant human interleukin 1 beta (IL-1 beta) and recombinant human interleukin-6 (IL-6) on spleen and bone marrow hematopoiesis in normal and cyclophosphamide-treated mice. Injection of IL-1 beta alone resulted in a significant increase in the number of granulocytes and splenic progenitors [burst-forming units-erythroid (BFU-E) and colony-forming units-granulomonocytic (CFU-GM)] as compared with control mice but did not markedly enhance the number of bone marrow BFU-E and CFU-GM. IL-6 alone had little effect on the number of splenic progenitors but significantly increased the number of marrow BFU-E and CFU-GM, especially after a 6-day cytokine treatment. Combined daily administration of IL-1 beta and IL-6 for 3 days resulted in a synergistic stimulation of hematopoiesis as evaluated by the number of spleen and bone marrow CFU-GM and BFU-E colonies. Likewise, IL-1 beta/IL-6 markedly enhanced the number of circulating neutrophils, whereas each cytokine alone had little or no effect. When the numbers of spleen progenitors and peripheral granulocytes were determined 1 day after the last injection, a synergistic myelostimulatory effect of combined IL-1 beta/IL-6 treatment was observed at all doses (IL-1 beta, 0.25-0.5 microgram; IL-6, 1-20 micrograms). Furthermore, combined treatment with IL-1 beta/IL-6 accelerated and potentiated the recovery of myeloid cells after cyclophosphamide injection, whereas the single regimen treatment was not effective. Particularly, the rebound of WBC (especially neutrophilic granulocytes) after cyclophosphamide treatment was markedly enhanced by the combined treatment, whereas the single regimen was ineffective. Altogether these results may contribute to the development of combination therapies with cytokines and antiblastic agents in the treatment of cancer patients.
我们研究了重组人白细胞介素1β（IL-1β）和重组人白细胞介素-6（IL-6）单独及联合治疗对正常小鼠和环磷酰胺处理小鼠脾脏及骨髓造血功能的影响。与对照小鼠相比，单独注射IL-1β可使粒细胞和脾脏祖细胞[红系爆式集落形成单位（BFU-E）和粒单系集落形成单位（CFU-GM）]数量显著增加，但对骨髓BFU-E和CFU-GM数量的增强作用不明显。单独使用IL-6对脾脏祖细胞数量影响较小，但可显著增加骨髓BFU-E和CFU-GM数量，尤其是在细胞因子治疗6天后。连续3天每日联合给予IL-1β和IL-6，通过脾脏和骨髓CFU-GM及BFU-E集落数量评估，可产生协同造血刺激作用。同样，IL-1β/IL-6可显著增加循环中性粒细胞数量，而单独使用每种细胞因子作用较小或无作用。在最后一次注射后1天测定脾脏祖细胞数量和外周粒细胞数量时，在所有剂量（IL-1β，0.25 - 0.5微克；IL-6，1 - 20微克）下均观察到联合IL-1β/IL-6治疗具有协同骨髓刺激作用。此外，IL-1β/IL-6联合治疗可加速并增强环磷酰胺注射后髓系细胞的恢复，而单一治疗方案无效。特别是，联合治疗显著增强了环磷酰胺治疗后白细胞（尤其是嗜中性粒细胞）的反弹，而单一治疗方案无效。总之，这些结果可能有助于开发细胞因子与抗增殖药物联合治疗癌症患者的方法。
