Page 107 - 2019_10 resto del Mondo_web

sHLH in LPS-treated SAMP/TA-1 mice
than in SAMR1 mice (Figure 7Ad and 7Bd). The fluctua- tion of the expression of IFN-g-inducible chemokine genes such as Cxcl9 and Cxcl10 in the liver and spleen of SAMP1/TA-1 mice paralleled that of IFN-g, which indicat- ed that functional IFN-g was produced in the liver and spleen. In several animal models of sHLH, IFN-g has been identified as a mediator of systemic inflammation and may play a pivotal role in the pathogenesis of sHLH, whereas the role of other cytokines is still not clear.36,37 IL- 1β, IL-6, and TNF-α are cytokines downstream of IFN-g in a mouse model of sHLH.36,37 Buatonis et al.36 demonstrated that in an sHLH model induced by repeated toll-like recep- tor 9 treatment, total IFN-g levels produced in tissues were 500- to 2,000-fold higher than those measured in blood, and they identified the liver and spleen as major sites of
A
IFN-g production. IFN-g may be a critical factor in the pathogenesis of sHLH in SAMP1/TA-1 mice. However, investigation of a therapeutic approach using antibodies for proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-g in mice is necessary to clarify the central factor(s) in the pathogenesis of sHLH-like disease in LPS- treated SAMP1/TA-1 mice.
Acute systemic inflammation augments myelopoiesis but suppresses B lymphopoiesis and erythropoiesis.22,38,39 Furthermore, acute systemic inflammation provokes rapid consumption of platelets, resulting in transient thrombo- cytopenia.40,41 The numbers of peripheral white blood cells, red blood cells, and platelets in SAMP1/TA-1 mice after repeated LPS treatment decreased rapidly compared with those in SAMR1 mice (Figure 1A). When BALB/c
B
Figure 8. The proportions of M1 and M2 peritoneal macrophages in SAMR1 and SAMP1/TA-1 mice after lipopolysac- charide treatment. (A; B) The changes in the proportions of M1 cells (CD11b+/iNOS+ cells) (A) and M2 cells (CD11b+/CD206+ cells) (B) in SAMR1 and SAMP1/TA-1 mice after the first treatment with 25 μg lipopolysaccharide (LPS) were evaluated. The samples of peritoneal macrophages were obtained from non-treated control mice (day 0) and mice 2 and 5 days after the first treatment with 25 μg LPS.
haematologica | 2019; 104(10)
2003