Severe
aplastic anemia (SAA) is a
rare disease characterized by severe
pancytopenia and
bone marrow failure. Most patients with AA respond to immunosuppressive therapy (IST), usually as
antithymocyte globulin (ATG) and
cyclosporine (CsA), but some relapse on CsA withdrawal or require long-term administration of CsA to maintain blood counts. Recent research has found that
rapamycin (Rapa) was an effective
therapy in mouse models of immune-mediated
bone marrow failure. However, it has not achieved a satisfactory effect in clinical application. At present, many studies have confirmed that
eltrombopag (ELT) combined with IST can improve the curative effect of AA patients. Then, whether Rapa combined Elt in the treatment of AA will acquire better efficacy than a single
drug application remains unclear. In this study, an immune attack-mediated AA mouse model was constructed by total body irradiation (TBI) and allo-lymphocyte infusion. In our study, we tested the efficacy of Rapa combined with Elt as a new treatment in mouse models of immune-mediated
bone marrow failure. It showed that treatment with Rapa in combination Elt in the AA mouse model ameliorated
pancytopenia and extended animal survival in a manner comparable to the standard dose of CsA and Rapa alone. However, there was no significant improvement effect on the number and function of NK cells and their subsets, mDCs, and CD4+/CD8+ ratio in AA mice after the
therapy of Rapa combined with Elt compared with Rapa alone. Furthermore, the secretion of
IL-10 of Tregs in AA mice increased significantly after the
therapy of Rapa combined with Elt, but there was no significant difference in the number of Treg cells. We did not observe the difference in the curative effect of the Rapa group and CsA group, but for IL-10/Tregs ratio, the Rapa group was superior to the CsA group. And the IFN-r secretion of CD8+T cells in AA mice decreased significantly after the combination
therapy of Rapa and Elt than Rapa alone. Compared with the AA group, the level of plasma IFN-γ,
IL-2, and TNF-α decreased significantly (P < 0.05), but
IL-10,
IL-4,
IL-5, and IL-1β increased significantly in the Rapa group (P < 0.05). As for
IL-10, IL-12p70,
IL-2,
IL-6, KC/GRO, and TNF-α, the
therapy of Rapa combined with Elt showed a more significant effect than Rapa alone in AA mice. To some extent, this study had shown a relatively better synergistic effect in murine models of immune-mediated
bone marrow failure after the combination
therapy of Rapa and Elt, which was a promising clinical utility in SAA treatment.