[Establishment of HLH-like mouse model with CPG-ODN and IFN-γ].

ABSTRACT

OBJECTIVE: To establish a hemophagocytic lymphohistiocytosis (HLH)-like mouse model induced by CpG oligodeoxynucleotide (CpG-ODN1826) and interferon (IFN)-γ for further study on therapy. METHODS: Wild type adult C57BL/6 mice were administered with PBS or CpG-ODN1826 (50 µg) by intraperitoneal injection every two day and IFN-γ subcutaneous injection every day. Parameters of HLH were evaluated on day 10. RESULTS: As compared to control, HLH-like symptoms in CpG group were characterized with pancytopenia accompanied by increased ratios of monocytes, alanine aminotransferase [(198.7±54.2)IU/L], triglyceride level [(12.1±0.6)g/L], and serum ferritin [(708.4±11.8)pmol/L]; decreased albumin [(217.7±4.3)g/L], fibrinogen [(17.1±1.9)g/L] (all P<0.05). Hepatosplenomegaly was obvious in CpG group. The liver in CpG group had multifocal hepatocytes necrosis and perivascular inflammations. Spleen had expanding red pulp and hyperplastic nucleated cells. Furthermore, macrophages in the liver and spleen were largely activated. Hemophagocytosis were observed in liver, spleen and bone marrow smear. The CpG group was alive during experiment, other than significant decreased activity after the first injection of CpG-ODN. CONCLUSION: These data demonstrate that repeated administration of CpG-ODN1826 and IFN-γ could induce HLH-like symptoms without fatal condition in wild type C57B/L mice. This protocol could establish a mild HLH-like mouse model, which could be useful for further study on HLH.