Abstract
Background: Atopic dermatitis (AD) is characterized by repetitious eczematous skin and is Th2 dominant in nature. Atopic dermatitis lesions have been observed to improve in patients during viral or bacterial infection, such as herpes simplex virus (HSV). A Th1 pathway established to counter viral infection may possibly be the mechanism for the relief of skin lesions in AD.
Methods: In animal AD models using NC/Nga mice, the effects of local intra- and/or subcutaneous injection of ultraviolet inactivated-HSV were examined for Th1/Th2 regulation through a negative regulation pathway with suppressor of cytokine signaling (SOCS)-3 and 5 using immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction.
Results: Lesional skin of HSV-treated mice displayed extensive interleukin (IL)-12p40-positive cellular infiltration compared with non-treated mice and IL-12p40/signal transducers and activators of transcription (STAT) 4/SOCS5 mRNA expression was noted basically the same in the three groups. Interleukin-4 receptor-positive cellular infiltrates in HSV-treated mice decreased significantly more than in non-treated mice and IL-4 mRNA expression in the three groups was essentially the same, but the expression of STAT6 and SOCS3 mRNA specific for the Th2 regulation pathway was reduced more in HSV-treated compared with non-treated mice. Expression of SOCS3 mRNA in situ in HSV-treated epidermis underwent a far greater reduction compared with expression in non-treated mice.
Conclusions: Ultraviolet-inactivated HSV treatment would appear to induce a Th1 cellular response and downregulate that of the Th2 pathway in AD-like lesions of NC/Nga mice by bringing about a reduction of SOCS3 expression in the skin. From the present results, certain HSV DNA components may be effective candidates for a new therapeutic approach in refractory AD.
