Biotin
Severe Fever with Thrombocytopenia Syndrome (SFTS), an emerging infectious disease caused by a novel phlebovirus, is associated with high fatality. Therapeutic interventions are lacking and disease pathogenesis is yet to be fully elucidated. The anti-viral immune response has been reported, but humoral involvement in viral pathogenesis is poorly understood. Here we show defective serological responses to SFTSV is associated with disease fatality and a combination of B-cell and T-cell impairment contribute to disruption of anti-viral immunity. The serological profile in deceased patients is characterized by absence of specific IgG to viral nucleocapsid and glycoprotein due to failure of B-cell class switching. Expansion and impairment of antibody secretion is a signature of fatal SFTSV infection. Apoptosis of monocytes in the early stage of infection diminishes antigen-presentation by dendritic cells, impedes differentiation and function of T follicular helper cells, and contributes to failure of the virus-specific humoral response.
In this study, we sought out to study the anti-cancer effects of propranolol (Pro) in combination with tumor lysate vaccine on lymphocyte proliferation activities as well as on IL-2, IL-4, IL-10, IL-12, IL-17 and IFN-? cytokine concentration in the tumor microenvironment (TME). A tumor model was established in inbred Balb/C mice using transplantation of tumor to the flank of native mice. Tumor-bearing mice were immunized with lysate tumor cells (vaccine), a combination of Pro/Vaccine (Vac). Control groups consisted of tumor-bearing mice receiving only propranolol or PBS three times with one week interval via subcutaneous (s.c) injection. One week after the last immunization, tumor was removed, homogenate was prepared and the levels of IL-12, IL-17, 1L-2, IL-10, IL-4, IFN-? cytokine concentrations were evaluated by commercial ELISA kits. In addition, spleen cell suspension was used for the lymphocyte proliferation assay using the BrdU method. Results from this study indicated that Pro/Vac had the ability to significantly increase lymphocyte proliferation, and to suppress tumor growth. Administration of breast tumor lysates with propranolol increased the concentration of IL-12, IL-17, 1L-2 and IFN-? cytokines in tumor microenvironment. This study has proved the efficiency of propranolol as an adjuvant in combination with the tumor vaccine model on tumor suppression via cytokine pattern modulation in tumor microenvironment.