Although membrane-bound Toll-like receptors (TLR2 and TLR4) are essential for lipopolysaccharide (LPS)induced TNF production [30] , this is not the case for Staphylococcus aureus. Because S. aureus is able to "attack" or form pores in macrophages, TNF secretion occurs even in the absence of TLR 2 and TLR4 sensors (possibly via Nod1 and Nod2, intracytoplasmic sensors of peptidoglycan-derived muropeptides) [31] . Therefore, another mechanism independent of Toll-like receptors must exist for ketamine's anti-inflammatory action, at least in staphylococcal infections.