Effect of Chronic Topical Exposure to Low‐Dose Noxious Chemicals and Stress on Skin Sensitivity in Mice

Abstract

Effect of Chronic Topical Exposure toLow-Dose Noxious Chemicals and Stress on Skin Sensitivity in Mice: Yumiko NAKANO. Department of Environmental Health, Osaka Prefectural Institute of Public Health-It has been suggested that the recent increase in inflammatory diseases is related to an increase in environmental chemicals and psychiatric stress. To investigate the effect of chronic topical exposure to chemicals and isolation stress, low-dose formalin (a mild contact sensitizer and an irritant), 2,4,6-trinitrochlorobenzene (TNCB; a potent contact sensitizer) and sodium lauryl sulphate (SLS; an irritant) were applied to mouse ears at 7-d intervals under nostress or stress conditions. Skin reactions (ear swelling) elicited by formalin and TNCB increased time dependently. At the chronic stage, a significant skin reaction peaking at 1 h after application was elicited on the formalin-treated sites, while a shift from a delayed-type hypersensitivity to an immediate-type response was observed on the TNCB-treated sites. At the formalin-treated sites, genes related to neurogenic inflammation, i.e., bradykinin (BK) B2 receptor, IL-6, and membrane metallo endopeptidase (NEP) mRNA were upregulated. In the TNCB-treated sites, marked upregulation of IFN-γ, IL-1β, IL-4, and IL-6 mRNA was observed in addition to B2 receptor mRNA. Pretreatment with HOE140, the B2 receptor antagonist suppressed these skin reactions. Increased skin sensitivity to an unrelated chemical, ethanol, and thermal stimuli were elicited in formalin and TNCBtreated mice. Cortisol levels in formalin-treated mice and IgE levels in TNCB-treated mice were elevated respectively. Stress markedly amplified the skin reactions and gene expression related to neurogenic inflammation. SLS did not induce any changes. It was concluded that chronic topical exposure to low-dose noxious chemicals and stress could easily induce skin sensitivity relating to the BK-B2 pathway and nociceptive sensitization reflecting neural sensitization. (J Occup Health 2007; 49: 431-442)

Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

“…Therefore, the outcome of corticosterone and epinephrine depends on their concentrations. Using a different contact sensitizing reagent (trinitrochlorobenzene) and isolation stress, Nakano also found that stress enhanced the cutaneous immune response as evaluated by ear swelling [72]. However, stress alone did not enhance the ear swelling response of mice treated with the contact irritant, sodium dodecyl sulfate.…”

Chronic psychological stress suppresses contact hypersensitivity: Potential roles of dysregulated cell trafficking and decreased IFN-γ production

“…In fact, ACD accounts for one of the highest rates of work-related skin disease (Karsak et al, 2007;Martin, 2012), and work-associated exacerbation of skin sensitivity is increasing in developed countries (Nakano, 2007). Contact hypersensitivity (CHS) is a model of this allergic response.…”

Causes, Mechanisms and Prevention of Environmental Diseases

“…First: elevated temperatures increase the solubility of PAHs and other lipophiles in water and also increase the vaporization of these species and hence result in higher air concentrations [271]. Second: elevated environmental temperatures accelerate the absorption of toxicants through respiratory, cutaneous and gastrointestinal routes and hence increase toxicity [210,[271][272][273]. Third; elevated temperatures increase thermal stress, impair heat stress response and delay unfolded protein recovery [274][275][276].…”