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Background and purpose:The macrophage-derived chemokine (MDC/CCL22) is a prototypic Th2-type chemokine intimately involved in Th2-skewed allergic diseases, such as atopic dermatitis and asthma. The statins (3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors) have been demonstrated to relieve allergic inflammation. However, the immunological effects and mechanisms of statins against atopic dermatitis remain unknown, at least in vitro. This study aimed to define how different statins affect MDC expression in HaCaT cells, a human keratinocyte cell line.

Atopic dermatitis (AD) is a chronically relapsing, pruritic, eczematous skin disorder accompanying allergic inflammation. AD is triggered by oxidative stress and immune imbalance. In the present study, we investigated the effect of drinking hydrogen water (HW) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in NC/Nga mice and found that HW ameliorated DNCB-induced AD-like clinical symptoms. In line with this, the level of reactive oxygen species in the HW group was significantly inhibited compared with that in the purified water (PW) group. In parallel, HW enhanced glutathione peroxidase activity in DNCBinduced AD as compared with the PW group. Accordingly, the levels of thymus and activation-regulated chemokine and cytokines were significantly decreased in the HW group compared with the PW group. Notably, the levels of Th 2 cytokine, interleukin-5 (IL-5), and proinflammatory cytokines such as tumor necrosis factor-α and IL-6 in HW-fed mice were significantly lower than in control and PW-fed mice. The total serum immunoglobulin E level was also markedly reduced in the HW group. The collective results indicate that HW suppresses DNCB-induced AD in NC/Nga mice via redox balance and immune modulation and could be a safe clinical fluid treatment for AD.Key words hydrogen water; atopic dermatitis; oxidative stress; immune modulation Atopic dermatitis (AD) is a chronically relapsing, pruritic, eczematous skin disorder accompanying allergic inflammation.1,2) AD is characterized by an impairment of the skinbarrier function, increased oxidative stress, and dysfunctional immune system. Intense infiltration of inflammatory cells release bioactive substance such as cytokines, chemokines, and reactive oxygen species (ROS).3) Of these AD's etiologic factors, inflammatory cytokines are known to regulate skin barrier, thereby aggravating the eczematous reaction in AD. 4)Most acute skin lesions in AD are exhibited by Th 2 inflammatory cytokines, whereas the chronic phase is characterized by Th 1 immune responses.5) The imbalance of cytokine network would play a critical role in the development of AD. 6,7)Together, oxidative stress such as increased ROS and lipid peroxidation is evident in any stage of AD. [8][9][10] An imbalance between ROS and antioxidants can lead to an elevated oxidative stress level. 11)Hydrogen molecule (H 2 ) has been widely used in medical applications as a safe and effective antioxidant and immunomodulator with minimal side effects.12-15) Unlike other antioxidants, which are unable to target organelles, H 2 can penetrate biomembranes and diffuse into the cytosol, mitochondria and nucleus. 13) Moreover, H 2 has been reported to have •OHscavenging activity in culture medium.14) Oral administration of hydrogen water (HW), inhalation of hydrogen gas, and injecting H 2 -dissolved saline is widely accepted to incorporate H 2 in the body. Recently, we reported that HW is effective in house mite-induced dermatitis via immunomodulation. 15) However, this study has a limitation owing to the lack of th...

Hydrogen water (HW) produced by electrolysis of water has characteristics of extremely low oxidation-reduction potential (ORP) value and high dissolved hydrogen (DH). It has been proved to have various beneficial effects including antioxidant and anti-inflammatory effects; however, HW effect on atopic dermatitis (AD), an inflammatory skin disorder, is poorly documented. In the present study, we examined the immunological effect of drinking HW on Dermatophagoides farinae-induced AD-like skin in NC/Nga mice. Mice were administered with HW and purified water (PW) for 25 days. We evaluated the serum concentration of pro-inflammatory (TNF-α), Th1 (IFN-γ, IL-2, and IL-12p70), Th2 (IL-4, IL-5, and IL-10), and cytokine expressed by both subsets (GM-CSF) to assess their possible relationship to the severity of AD. The serum levels of cytokines such as IL-10, TNF-α, IL-12p70, and GM-CSF of mice administered with HW was significantly reduced as compared to PW group. The results suggest that HW affects allergic contact dermatitis through modulation of Th1 and Th2 responses in NC/Nga mice. This is the first note on the drinking effect of HW on AD, clinically implying a promising potential remedy for treatment of AD.

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