Marginal zone (MZ) B cells produce a first wave of antibodies for protection from blood-borne pathogens. However, the role of MZ B cells in inflammatory responses has not been elucidated. Here we show that MZ B cells produce pro-inflammatory cytokines, such as interleukin-6 (IL-6), and exacerbate systemic inflammatory responses to lipopolysaccharide (LPS). After intravenous injection of LPS or E. coli, mice deficient in MZ B cells or IL-6 only in MZ B cells have attenuated systemic inflammatory responses and prolonged survival compared with wild-type mice. LPS directly stimulates MZ B cells via Toll-like receptor 4 (TLR4) and MyD88 pathways for IL-6 production. Furthermore, TLR4 requires physical and functional association with Fcα/μR (CD351) for its oligomer formation, NF-κB signalling and IL-6 production from MZ B cells; this association is responsible for systemic inflammatory responses and endotoxic shock. These results reveal a pro-inflammatory role of MZ B cells in endotoxic shock.
Chylothorax is an abnormal condition of lymphatic fluid collection in the pleural space, and the somatostatin analog octreotide is thought to have a beneficial effect on chylothorax. However, the octreotide dosage and administration route for chylothorax have been inconsistent to date. We report three neonatal cases of persistent chylothorax successfully treated with high-dose octreotide infusion therapy (20 μg/kg/h). Case 1 was congenital chylothorax, Case 2 was secondary chylothorax after an operation for congenital diaphragmatic hernia, and Case 3 was chylothorax after a cardiac operation. In all cases, the chylothorax was not decreased by a low-dose octreotide infusion, but after a high-dose octreotide infusion, the chylothorax decreased and eventually vanished, with no side effects. Conclusion: We suggest that the dose of octreotide in neonatal chylothorax can be safely increased to a maximum of 20 µg/kg/h.
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