Differences in cytokine stimulation between methicillin-susceptible and methicillin-resistant Staphylococcus aureus in an experimental endocarditis model

The present study focused on the impact of methicillin resistance of Staphylococcus aureus on cytokine production by monocytes. Cytokine stimulation was studied by 20 heat-killed isolates, 10 methicillin-susceptible Staphylococcus aureus (MSSA) and 10 methicillin-resistant Staphylococcus aureus (MRSA). Bacterial endocarditis was induced in 27 male rabbits by challenge with 1 MSSA isolate and 1 MRSA isolate. Blood was sampled for estimation of tumor necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) and stimulation of monocytes. MSSA induced greater stimulation of TNF-alpha than MRSA, as shown after addition of a Toll-like receptor-4 (TLR4) antagonist. Survival of rabbits challenged by MRSA was prolonged compared to those challenged by MSSA. Serum MDA was greater after MSSA stimulation. Serum of animals challenged by MRSA stimulated greater release of interleukin (IL)-8 and IL-10 compared with MSSA: the opposite was observed for TNF-alpha. It is concluded that MSSA and MRSA induce a different pattern of TNF-alpha stimulation through a TLR4-independent mechanism, leading to shorter survival in experimental endocarditis.