ABSTRACT
Objective The secretion level of inflammatory factors is closely related to the severity of severe fever with thrombocytopenia syndrome (SFTS). This paper mainly discussed the effect of SFTSV infection on the expression of Toll-like receptor 2（TLR2） and inflammatory factors in macrophages in mice. Methods The expression of TLR2 andTNF-α, IFN-β, IL-6, IL-10 and other inflammatory factors were observed at 0, 6, 12, 24, 36, 48, 72 hours after SFTSV infected mice macrophages by qPCR, Western blot and ELISA. Results QPCR results showed that the mRNA levels of TNF-α at 0, 6, 12, 24, 36, 48, 72 h were 0.85±0.14, 15.23±2.45, 28.67±1.59, 94.52±7.05, 55.86±1.82, 23.55±6.15, 9.76±2.03, and the mRNA levels of IFN-β were 0.93±0.21, 1.55±0.33, 14.51±1.98, 55.16±3.64, 26.57±1.49, 9.22±0.51, 5.18±1.06. QPCR results showed that the mRNA levels of TNF-α and IFN-β produced by abdominal macrophages in the infected mice showed a trend of first increasing (the highest at the 24 hour) and then decreasing, and the difference of TNF-α and IFN-β mRNA levels at other time points was statistically significant compared with that at the 0 hour (P<0.05). However, IL-6 and IL-10 mRNA levels continued to increase, and the difference at other time points was statistically significant (P<0.05). ELISA results showed that the expression of four inflammatory factors showed a trend of gradual increase: TNF-α 0 and 72 h were (38.31±4.25, 140.41±23.45) pg/mL; IFN-β 0th and 72th were (17.56±0.66, 1084.93±111.42) pg/mL; IL-6 protein 0 and 72 h were (113.30±0.07, 2302.32±134.09) pg/mL; IL-10 protein 0 and 72 h were (515.00±21.21, 2590.40±226.19) pg/mL, respectively, with significant increases at the 24, 36, 48 and 72 hours compared with that at the 0 hour (P<0.05). The expression of TLR2 mRNA generated by mouse peritoneal macrophages showed a trend of first increasing and then decreasing, and increased to the highest level at 24 h, and the difference between each time point and 0 h was statistically significant (P<0.01). The expression of TLR2 gradually increased after infection with time extension. Conclusion SFTSV infection can up-regulate the expression of TLR2 in macrophages, thereby leading to the increased secretion of the cytokines.
ABSTRACT
Pharmacokinetic parameters can be significantly altered for acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO) and continuous veno-venous hemofiltration therapy (CVVH). Here we reported a case of individualized vancomycin dosing for a patient diagnosed as severe acute pancreatitis treated with concurrent ECMO and CVVH. A 65 kg 32-year-old woman was admitted to hospital presented with severe acute pancreatitis (SAP), respiratory failure, metabotropic acidosis and hyperkalemia. She was admitted to intensive care unit (ICU) on hospital day 1 and was initiated on CVVH. She progressed to multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) on ICU day 2, and veno-venous ECMO was instituted. Several catheters were inserted into the body to support ECMO, CVVH and pulse indicator continuous cardiac output (PiCCO), so vancomycin was prescribed empirically on ICU day 3 for prevention of catheter-related infection. Given the residual renal function and continuous hemofiltration intensity on day 3, vancomycin bolus of 1 000 mg was prescribed, followed by a maintenance dose of 500 mg every 8 hours. On ICU day 4, a vancomycin trough serum concentration of 14.1 mg/L was obtained before the fourth dose, which was within the target range of 10-20 mg/L. By ICU day 7, vancomycin dosage was elevated to 1.0 g every 12 hours because of aggravated infection and improved kidney function. On ICU day 14, a vancomycin trough serum concentration of 17 mg/L was obtained. Her white blood cell (WBC) and neutrophil percentage (Neut%) dropped to the normal level by ICU day 19. This vancomycin regimen was successful in providing a target attainment of trough serum concentration ranging from 10-20 mg/L quickly and in controlling infection-related symptoms and signs properly. With the help of this case report we want to call attention to the clinically significant alteration in vancomycin pharmacokinetics among critically ill patients. Individualized vancomycin dosing regimens and therapeutic drug monitoring are necessary for critically ill patients receiving CVVH and ECMO to ensure that the target serum vancomycin levels are reached to adequately treat the infection and avoid nephrotoxicity.