Meticillin-resistant Staphylococcus aureus infection in diabetic mice enhanced inflammation and coagulation

Abstract

BALB/cA mice were used to study the interaction of diabetes and meticillin-resistant Staphylococcus aureus (MRSA) infection on pathogen distribution, cytokine profile and inflammatory and endothelial-injury markers, as well as coagulation and anticoagulation factors. Meticillin-susceptible S. aureus (MSSA) infection did not cause death within the experimental period. MRSA-infected nondiabetic and diabetic mice died on 19·1±1·4 and 10·6±0·7 days post-infection (p.i.), respectively. MRSA and MSSA infection in diabetic mice did not result in symptomatic bacteraemia; however, MRSA infection in diabetic mice significantly reduced glucose levels (P<0·05). Diabetic mice showed significantly higher levels of C-reactive protein, fibrinogen, fibronectin and von Willebrand factor than nondiabetic mice (P<0·05), and MRSA infection further elevated the plasma levels of these inflammatory and endothelial markers (P<0·05). Before infection, diabetic mice had significantly higher plasminogen activator inhibitor-1 (PAI-1) activity, lower antithrombin III (AT-III) and protein C activities (P<0·05), and MRSA infection significantly increased PAI-1 activity further and reduced the activity of AT-III and protein C (P<0·05). MRSA infection increased the production of three Th1 cytokines, interleukin 2 (IL-2), tumour necrosis factor alpha and gamma interferon, in diabetic mice (P<0·05); however, three Th2 cytokines, IL-4, IL-6, IL-10, were elevated at 2 and 4 days p.i., and then dropped gradually. MRSA infection in diabetic mice accelerated the inflammation process, endothelial injury and blood coagulation in diabetic mice. Therefore, the development of proper infection diagnosis and timely use of effective treatments for MRSA-infected diabetic individuals is important and necessary.