Of reported occupational injury associated with workman's compensation, contact dermatitis ranks second most prevalent over all. Inflammatory cytokines are known to be closely involved in dermatitis, and modulation of various cytokines by specific irritants could exacerbate skin damage contributing to increased irritancy. If specific cytokines can be associated with irritancy, this may be of significant predictive value when judging the irritancy potential of a chemical, or the response of an individual to irritant exposure. Interestingly JP-8 jet fuel, which is non-corrosive yet causes severe irritant dermatitis, decreases the expression of the inflammatory cytokine IL-6 in exposed skin. Because IL-6 is paradoxically associated with both skin healing and inflammation, it may be that chemically induced, or genetically associated modulation of skin IL-6 levels contributes to severity of dermatitis. To investigate this, the skin of IL-6 deficient (KO), IL-6 over-expressing transgenic (Tg), and wild type (WT) mice was exposed to the irritants JP8 jet fuel, benzalkonium chloride, and acetone as a control. Skin samples were collected after up to 7 days of exposure and were assessed for inflammation by visualization of dermatoses, histopathology, and inflammatory cytokine expression. It was found that KO mice displayed significantly greater levels of inflammation as compared to WT and Tg mice. By 7 days, there is a nearly six-fold increase in inflammatory M1 macrophages in JP8 treated IL-6KO skin, while no increase was apparent in Tg skin. Similarly, the expression of the inflammatory cytokines IL-1, CCL3, CCL11, and CCL20 was increased 4-6 fold after seven days of JP8 treatment in KO skin, where very small changes were apparent in Tg skin. These data indicate that IL-6 is indeed not pro-inflammatory in skin, but rather is associated with resistance to irritancy. Thus, IL-6 could prove to be a useful marker in determining irritancy potential of a chemical or susceptibility of an individual to irritant dermatitis.
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC