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 toxicity, increased concern has been placed on topical exposures due to reports of severe contact dermatitis among military personnel. All three of the predominant aviation fuels currently used by the commercial and military sectors have been demonstrated experimentally to induce the production of interleukin-8 (IL-8), a proinflammatory cytokine, in normal human epidermal keratinocytes (NHEK). The objective of this study was to examine the effects of individual hydrocarbon components found in these fuels on IL-8 production by NHEK. In order to circumvent the extreme hydrophobicity of these compounds, 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 microM. These hydrocarbons caused a peak in IL-8 release at a concentration of 31.2 microM, with the exception of dodecane which peaked at 62.5 microM. Subtoxic concentrations of the aliphatic hydrocarbons were those < 62.5 microM. These studies demonstrate that the etiology of proinflammatory cytokine expression due to jet fuel exposure may be due in large part to the aliphatic hydrocarbon components. Furthermore, these studies provide additional evidence that hydrocarbons can be successfully delivered to cells in culture by encapsulating them in cyclodextrin inclusion complexes.
Allen
D G
DG
Center for Cutaneous Toxicology and Residue Pharmacology, North Carolina State University, Raleigh, NC 27606, USA.
Riviere
J E
JE
Monteiro-Riviere
N A
NA
D002478:Cells, Cultured; D003505:Cyclodextrins / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D006838:Hydrocarbons / Q000737:chemistry / Q000633:toxicity*; D016209:Interleukin-8 / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007648:Kerosene / Q000633:toxicity*; D012995:Solubility; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D004337:Drug Carriers; D006838:Hydrocarbons; D016209:Interleukin-8; D007648:Kerosene; D047391:alpha-Cyclodextrins; C032613:alpha-cyclodextrin