Low Dose Interleukin-2in The Treatment Of Acquired Hemophagocytic Syndrome

Objective Hemophagocytic syndrome (HPS), is also called hemophagocytic lymphohistiocytosis (HLH), shows symptoms of disease severity, rapid development,has a high mortality and need require timely clinical interventions. The mainsymptoms of HPS include persistent fever, peripheral cytopenias, hepatosplenomegaly, abnormal liver function, dysfunction of coagulation, hypertriglyceridemia,hypercytokinemia, methemoglobinemia and so on. Histopathology shows that quantity different hemophagocytes in the organs of bone marrow, liver, lymph nodes and the name comes. Now it is considered that the pathogenesis of HPScorrelates closely with dysimmunity; the histopathology changes in HPS, suchas phagocytes accumulation in bone marrow, liver, spleen, lymph nodes causethe injure of tissues and organs, are related to the functional impairment of nature killer cells (NK) and cell toxicity T lymphocytes (CTL). Stimulation of continued antigen to immunocyte, such as macrophage, T lymphocyte, leads tovarious cytokines produced; overactivation of helper T cell1(Th1), imbalancebetween Th1and helper T cell2(Th2), production of the amount of cytokines such as Interferon-γ(IFN-γ), Interleukin-6(IL-6), Interleukin-10(IL-10), cytokine storm, macrophage phagocytic function further enhanced leads to HPS. The clinical manifestations of HPS almostly stem from hypercytokinemia so thatprompt control that could gain enough time for treatment. Regulatory T cell (Treg) represents immunosuppression of overactivation of immunocyte，autoimmune reaction etc and plays a key role in maintaining immune tolerance and immune homeostasis. Interleukin-2as a cytokine can stimulate the activation andproliferation of effector T cell at the time of high dose treatment, however, pr eferentially stimulate Treg and enhance the function of CD8+T and NK cellswhen low dose and continuous low dose IL-2receiving,respectively. So to increase the function of Treg, suppress the activation of immunocyte and inhibit cytokine storm may gain the goal in improvement and treatment of HPS. The thesis conducts a research on the continuous low dose IL-2treatment in acquired HPS patients, compared with those receiving immunosuppressive therapy, and further explores the effect of low dose IL-2on the immunologic function in acquired HPS patients and the therapeutic value.Methods According to HPS diagnostic criteria recommended by the World HealthOrganization in2004,6patients with acquired HPS newly diagnosed were evenlydivided into IL-2group and the control group. IL-2group continued application of lowdose of IL-2(1million units), once a day, subcutaneous injection,3patients treatedwith immunosuppressant as control group. Meanwhile, the two groups both combinedwith anti-infection, hormones and other conventional treatment. Next, the changes ofclinical symptoms and signs, blood count, liver function, cellular immune function andother clinic indicators were regular observed before and after treatment. Finally, weanalyzed and summarized the therapeutic effect and mechanism of low dose of IL-2onHPS.Results The indicators of the cellular immune function of6patients, with acquired HPSnewly diagnosed, were significantly lower than the normal range, which indicated theyall were in the severe immune deficiency states..IL-2group: The temperature and routine blood quickly began to recover in one patientwith treatment of low dose of IL-2. Routine blood and liver function returned to normalafter4weeks. But the patient repeated and deteriorated because of stopping drug, andthen died of multiple organ failure in143days. The temperature returned to normal in1 week, liver function, triglycerides and fibrinogen were basically maintain normal inother two patients. But the routine blood of the two patients have not been back tonormal, and they finally died of bleeding. The expression of Treg and Treg/Teff ratiowere significantly increased in two patients of IL-2group. But the other one Patientwith IL-2treatment has no significant changes on the expression of Treg and Teff.Control group: One patient secondary to adult Still’s disease, died in3days afterdiagnosis; patients. The second patient’s temperature is back to normal after8days, butonly for10days. But routine blood has always been abnormal in the course of treatment,and then, the patient died of fungal infection in38days. The last patient’s temperatureis also back to normal after treated with the large doses of hormones, and only for13days. But the patient also unfortunately died of a serious intestinal fungal infection in55days.Conclusion Low-dose of IL-2therapy, to some extent, improve the immune function,and the clinical signs and laboratory parameters for the HPS patients. The application oflow dose of IL-2on regulation of the immune system, may provide new ideas for thetreatment of HPS, especially for infection related HPS.