Differential relationship between the carbon chain length of jet fuel aliphatic hydrocarbons and their ability to induce cytotoxicity vs. interleukin-8 release in human epidermal keratinocytes

Jet fuels are complex mixtures of hydrocarbons known to cause dermal toxicity and to increase the release of proinflammatory cytokines by human epidermal keratinocytes (HEK). However, the dermatotoxic effects of individual hydrocarbons remain unclear. Since aliphatic hydrocarbons make up more than 80% of the hydrocarbons formulated in jet fuels, the objective of this study was to assess acute cytotoxicity and IL-8 release induced by individual aliphatic hydrocarbons without a vehicle. Ten aliphatic hydrocarbons with carbon (C) chain lengths ranging from 6 to 16 were dosed neat on HEK grown on 96-well plates. Acute exposure (1, 5, and 15 min) to aliphatic hydrocarbons significantly increased HEK mortality such that the increase in cytotoxicity corresponded with the decrease in carbon chain length. Extended exposure time did not increase cytotoxicity significantly until 15 min of exposure by short-chain hydrocarbons (C less than or equal to 11). There were differences between the aliphatic hydrocarbons with respect to their effects on IL-8 release. IL-8 concentration was increased significantly by 3- to 10-fold, with the highest increase found after exposure to hydrocarbons in the C9-C13 range. These studies indicated that individual aliphatic hydrocarbons are toxic to HEK cells and are capable of inducing proinflammatory cytokines. Higher cytotoxicity by shorter-chain aliphatic hydrocarbons did not correlate to increased ability to stimulate IL-8 release, which peaked at mid-chain lengths, suggesting a different structure-activity relationship for these two toxicological endpoints in keratinocyte cell cultures.