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Background: The characteristic feature of immune cytopenias involves the process of extravascular phagocytosis, wherein macrophages in the spleen and/or liver engage in the destruction of blood cells that have been opsonized by auto‐ or alloantibodies. Therefore, new treatments that prevent phagocytosis will be advantageous, especially for short‐term usage along with alternative options. Study Design and Methods: KB‐208, a small molecule drug, previously shown to be efficacious for the in vitro inhibition of phagocytosis was synthesized. A passive antibody mouse model of immune thrombocytopenia (ITP) was used. Three different mouse strains (BALB/c, C57BL/6, CD1) were used to determine the efficacy of KB‐208 compared with IVIG to ameliorate the ITP. Toxicity was investigated after 60‐day chronic administration of KB‐208 by a biochemistry panel, gross necroscopy and histopathology. Results: KB‐208 showed similar efficacy to ameliorate the thrombocytopenia compared with IVIG in all three mouse strains. This small molecule drug was effective at 1 mg/kg in ameliorating ITP, in comparison with IVIG at 1000–2500 mg/kg. KB‐208 did not affect other blood parameters or elevate serum biochemistry markers of toxicity nor were any abnormal histopathological findings found. Conclusion: KB‐208 is similar to IVIG for the amelioration of ITP in multiple mouse strains. Chronic administration of KB‐208 for 60 days did not demonstrate in vivo toxicity. These findings indicate that KB‐208 is efficacious, without significant in vivo toxicities in mice, and is a potential small molecule candidate for further evaluation to be used in the treatment of ITP and possibly all immune cytopenias where phagocytosis is responsible for the pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune/inflammatory disease. The heterogeneity and complexity of clinical presentation has made it challenging to study or treat this syndrome. The (NZW×BXSB) F1 lupus-prone male mouse model of this disease is potentially useful to study mechanism and treatment modalities, but there is a lack of information about this model's characterization and disease progression. Therefore, the aim was to examine this lupus model's physical/clinical disease presentation and its immunological status. Materials and Methods: Clinical and physical status were observed in 8- and 16-week-old male and female (± 1 week) (NZW/LacJ x BXSB/MpJ) F1 mice (n = 8 per group). Young males (8 ± 1 week) without disease and female (16 ± 1 week) mice served as controls. Physical changes, quantitative values of autoantibodies, and blood cell parameters were determined. Necropsy and post-mortem histopathology were also performed. Results: With aging (≥ 12 weeks), significant increases in severe abdominal distension/swelling, inability to walk, paleness of paws and significant weight increase were observed compared to controls (p < 0.05). The necropsy examination showed abdominal distension associated with serous effusion and histological examination identified severe edema and multi-organ abnormalities (spleen, lymph nodes, and kidney). Significant increases in anti-double-stranded DNA antibody (anti-dsDNA) was seen in old/sick compared to female (p = 0.0002) or young male (p = 0.0036) mice. Old mice developed immune thrombocytopenia compared to female (p = 0.0056) and young male (p = 0.0007) mice. Anti-platelet was detectable in old, sick mice. The mortality rate increased with aging; more than 35% of male mice died during this study between the ages of 13-18 weeks. Conclusion: We found that the (NZW/LacJ x BXSB/MpJ) F1 male mice spontaneously exhibit, over varying lengths of time, extremely severe and fatal clinical disease symptoms. This model may be too severe to be helpful in investigating SLE and testing potential treatment modalities. [ABSTRACT FROM AUTHOR]