TLR4 and Heat Stroke: Gram-negative sepsis is also clinically similar to heat stroke. This is not coincidental since both are considered forms of SIRS. The pathogenesis of gram-negative sepsis and heat stroke involves a PAMP (gram-negative endotoxin or LPS) and a DAMP (circulating HSP72) that interact with toll-like receptor-4 (and TLR-2) [12,13,57].