Artificial human skin: cytokine, prostaglandin, Hsp70 and histological responses to heat exposure

Artificial human skin, Skin(2)(TM) (keratinocytes and fibroblasts) and EpiDerm(TM) (keratinocytes), was used to determine heat-induced release/accumulation of mediators of injury and repair. Skin(2) was exposed to 37 or 41-45 degrees C for 90 min, followed by 37 degrees C for 22.5 h. Media were analyzed for interleukin-1 alpha (IL-1 alpha), prostaglandin-E, (PGE), thromboxane-B-2 (TxB(2)) and nuclear matrix apparatus protein (NMAP, viability). Specimens were taken for microscopy. Media and lysates from Skin(2) and EpiDerm (37 and 45 degrees C) were analyzed for IL-1 alpha, its soluble receptor (sIL-1RII), receptor antagonist (IL-1Ra), interleukin-6 (IL-6) and heat shock protein-70A (lysates only). Significant release of IL-1 alpha and PGE, was detected only above 43 degrees C, where viability deteriorated and histological damage (especially to keratinocytes) was observed. With both skin products, sIL-1RII release was heat-depressed. IL-1 alpha and IL-1Ra were elevated in media and IL-1Ra appeared to lower the bioactivity of IL-1 alpha. Heat depressed IL-6 release from Skin(2) fibroblasts. IL-6 production and release were negligible with EpiDerm. Heat increased Hsp-70A in both products. We conclude keratinocytes and fibroblasts are not primary cytokine and prostaglandin sources in heatstroke ( < 44 degrees C) but could be in evaporative cooling failure, focal hot spots, or systemic responses. Levels of IL-1Ra. PGE(2) and Hsp70A may be important markers of cell status. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.