Analysis of interleukin-8 release from normal human epidermal keratinocytes exposed to aliphatic hydrocarbons: delivery of hydrocarbons to cell cultures via complexation with alpha-cyclodextrin

While inhalation exposures represent the predominant route for jet fuel tox icity, increased concern has been placed on topical exposures due to report s of severe contact dermatitis among military personnel. All three of the p redominant aviation fuels currently used by the commercial and military sec tors have been demonstrated experimentally to induce the production of inte rleukin-8 (IL-8), a proinflammatory cytokine, in normal human epidermal ker atinocytes (NHEK). The objective of this study was to examine the effects o f individual hydrocarbon components found in these fuels on IL-8 production by NHEK. In order to circumvent the extreme hydrophobicity of these compou nds, inclusion complexes were formed between alpha -cyclodextrin/aliphatic hydrocarbons by adding 2 mM hydrocarbons to 4 mM alpha -cyclodextrin. NHEK were exposed to four aliphatic hydrocarbons (undecane, dodecane, tridecane, hexadecane) for 24 h at concentrations of 7.8-500 muM. These hydrocarbons caused a peak in IL-8 release at a concentration of 31.2 muM, with the exce ption of dodecane which peaked at 62.5 muM. Subtoxic concentrations of the aliphatic hydrocarbons were those < 62.5 muM. These studies demonstrate tha t the etiology of proinflammatory cytokine expression due to jet fuel expos ure may be due in large part to the aliphatic hydrocarbon components. Furth ermore, these studies provide additional evidence that hydrocarbons can be successfully delivered to cells in culture by encapsulating them in cyclode xtrin inclusion complexes. (C) 2001 Elsevier Science Ltd. All rights reserv ed.