Sredni B, Rosenthal-Galili Z, Michlin H, Sobelman D, Seger Y, Blagerman S, Kalechman Y, Rager-Zisman B
C.A.I.R. Institute, Marilyn Finkler Cancer Research Center, Bar Ilan University, Ramat Gan, Israel.
Immunol Lett. 1994 Dec;43(3):159-65. doi: 10.1016/0165-2478(94)90217-8.
Infection with cytomegalovirus (CMV) continues to be one of the most common complications following allogeneic bone marrow transplantation. The gravest danger for the host occurs when the virus is reactivated as a result of immunosuppression. In this report we studied the effects of sublethal murine cytomegalovirus (MCMV) infection on the hemopoietic system including bone marrow (BM) cellularity, production of colony stimulating factor (CSF) and interleukin-6 (IL-6) and the development of granulocyte-macrophage colony forming units (CFU-GM), and BM stromal cell viability. Our findings show that the virus infection led to a significant decrease in the number of BM cells and in the production levels of CSF and IL-6. There was also a decrease in the number of stromal cells, as reflected by the number of colony forming unit fibroblasts (CFU-F), and in the relative number of CFU-GM progenitors. Treatment of MCMV infected mice with the immunomodulator AS101 [ammonium trichloro (dioxyethylene 0-0')tellurate] restored significantly CSF and IL-6 production by BM cells to levels of uninfected control mice as well as the number of CFU-F and stromal cell elements which consequently led to the restoration of the total number of BM cells. Results presented here indicate that AS101 may have immunomodulatory effects on MCMV mediated myelosuppression. Administration of AS101 to patients with CMV associated BM damage may improve the restoration of their BM function.
巨细胞病毒(CMV)感染仍然是异基因骨髓移植后最常见的并发症之一。当病毒因免疫抑制而重新激活时,宿主面临的危险最为严重。在本报告中,我们研究了亚致死剂量的鼠巨细胞病毒(MCMV)感染对造血系统的影响,包括骨髓(BM)细胞数量、集落刺激因子(CSF)和白细胞介素-6(IL-6)的产生、粒细胞-巨噬细胞集落形成单位(CFU-GM)的发育以及BM基质细胞活力。我们的研究结果表明,病毒感染导致BM细胞数量以及CSF和IL-6的产生水平显著下降。基质细胞数量也有所减少,这通过成纤维细胞集落形成单位(CFU-F)的数量以及CFU-GM祖细胞的相对数量得以体现。用免疫调节剂AS101 [三氯(二氧乙烯0-0')碲酸铵] 治疗MCMV感染的小鼠,可使BM细胞产生的CSF和IL-6显著恢复到未感染对照小鼠的水平,同时使CFU-F和基质细胞成分的数量恢复,从而导致BM细胞总数的恢复。此处呈现的结果表明,AS101可能对MCMV介导的骨髓抑制具有免疫调节作用。对CMV相关BM损伤患者给予AS101可能会改善其BM功能的恢复。