Hyperthermia increases the cytotoxicity of many exogenous compounds.
Cytotoxicity testing of extracts from medical device materials is typically conducted at 37 degrees C. It may be more relevant to screen extracts from device materials for in vitro cytotoxicity at temperatures found in febrile patients. To address this, the cytotoxicity of selected chemicals, drugs, and medical device extracts was evaluated in vitro following incubation at normothermic (37 degrees C) and hyperthermic (39 degrees C) conditions. In L929 cells, the percentage of cell death increased from 2-fold to more than 4-fold after chemical exposure when cells were maintained at 39 degrees C. Extracts of some medical devices and materials showed a 10-fold increase in cytotoxicity when cells were maintained at 39 degrees C as compared to 37 degrees C. For many of the substances in this study, exogenous compounds that are toxic at normothermic conditions (37 degrees C) are more cytotoxic under hyperthermic conditions (39 degrees C). The toxicity of compounds was more readily discernable at the higher incubation temperature, even at lower concentrations. In vitro cytotoxicity testing of chemicals and extracts at febrile temperatures can provide more sensitive and relevant biocompatibility tests than under normothermic conditions alone.
Lucas
Anne D
AD
US Food and Drug Administration, Center for Device and Radiological Health, Silver Spring, MD 20903, USA. anne.lucas@fda.hhs.gov
Lappalainen
Sharon K
SK
Wray-Cahen
Diane
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D006358:Hot Temperature; D006801:Humans; D019169:Jurkat Cells; D008670:Metals / Q000008:administration & dosage*; D051379:Mice; D009930:Organic Chemicals / Q000008:administration & dosage*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*
D008670:Metals; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations