Exposure to cold First, exposure to cold and the subsequent rewarming to normal body temperature may influence the inflammatory response through the release of immunomodulatory danger associated molecular patterns (DAMP`s), more specifically TLR-4 ligands such as heat shock protein 70 (HSP-70). It was shown that HSP-70 mRNA levels in isolated cardiac myocytes increased during rewarming after 2.5 hours of hypothermia. Furthermore, pre-incubation of human cells exposed to 4 °C for 1, 2, 3 and 4 hours induced synthesis and accumulation of HSP-70 upon recovery to 37 °C. The relevance of HSP-70 for the inflammatory response is evident from a study in which HSP-70 was shown to induce potent anti-inflammatory effects resembling induction of endotoxin tolerance in human monocytes.