The Combined Use of Cytokine-Induced Killer Cells and Cyclosporine A for the Treatment of Aplastic Anemia in a Mouse Model

Abstract

In this study, we investigated the combined use of cytokine-induced killer (CIK) cells and cyclosporine A (CsA) to treat a mouse model of aplastic anemia (AA). CIK cells were cultured and injected alone or in combination with CsA into mice that had previously been induced into AA by busulfan and mouse interferon-γ (IFN-γ). The CIK cell-treated group had a survival rate of 55%, which was similar to the 60% survival rate observed in the CsA-treated group. The combination group showed a survival rate as high as 90%, while none of the mice in the no-treatment group survived to the end of the experiment. The CIK cells produced multiple cytokines, including several hematopoietic growth factors, which could promote the expansion of mouse bone marrow mononuclear cells in vitro. CsA reduced the proportion of CD4(+) T cells and the level of IFN-γ. The combined CIK cell and CsA treatment exhibited the best curative effect, a finding that might be due to the influence of these factors on both hematopoiesis and immunity. These data suggest that the combination of CIK cells and immunosuppressive therapy might be a candidate therapy for AA in the future.

In-vitro influence of mycophenolate mofetil (MMF) and Ciclosporin A (CsA) on cytokine induced killer (CIK) cell immunotherapy

“…Regarding cytokine/chemokine secretion, we observed no significant differences between CIK cells with and without MPA treatment expect for a significant reduction in TNFα secretion. These results are in accordance with Liu et al [ 36 ] who published promising results combining CIK cell therapy with CsA treatment also describing the secretion of various cytokines including IL-2 and IL-8. In contrast, Brehm et al [ 9 ] and Nagy et al [ 37 ] reported a significant reduction in the secretion of IFNγ, IL-6 and other cytokines by NK cells upon MPA treatment, but here immune cells were co-incubated with MPA already during cultivation time.…”

Therapeutic efficacy of cyclosporin A against spinal cord injury in rats with hyperglycemia

“…It is released from mitochondria and translocates to nuclei, followed by the induction of chromatin condensation and DNA degradation during cell apoptosis ( 37 ). To date, previous studies have indicated that CsA has a therapeutic effect on a number of diseases through various pathways, including reducing the proportion of CD4(+) T cells and the expression level of interferon-i for the treatment of aplastic anemia ( 38 ). Guan et al ( 39 ) demonstrated that CsA has a protective effect in improving mitochondrial function through inhibiting mitofusin proteins, which are located on the outside of mitochondrial membranes and regulate mitochondrial fusion.…”