Anti-inflammatory effect of fullerene C60 in a mice model of atopic dermatitis.

BACKGROUND: Water-soluble form of fullerene C60 is a promising tool for the control of ROS-dependent inflammation including allergic diseases. Anti-inflammatory effects of C60 (nC60) aqueous dispersion were evaluated in the mouse models of atopic dermatitis using subcutaneous (SC) and epicutaneous (EC) applications during 50 days period. A highly stable nC60 was prepared by exhaustive dialysis of water-organic C60 solution against water, where the size and ζ-potential of fullerene nanoparticles are about 100 nm and -30 mV, respectively. RESULTS: To induce skin inflammation, female BALB/c mice were EC sensitized with ovalbumin three times during one-weekly exposures. The nC60 solution was administrated in mice subcutaneously (SC) (0.1 mg/kg) and epicutaneously (EC) (1 mg/kg). Significant suppression of IgE and Th2 cytokines production and a concomitant rise in concentrations of Th1 cytokines were observed in nC60-treated groups. In addition, a significant increase in the levels of Foxp3(+) and filaggrin mRNA expression was observed at EC application. Histological examination of skin samples indicated that therapeutic effect was achieved by both EC and SC treatment, but it was more effective with EC. Pronounced reduction of the eosinophil and leukocyte infiltration in treated skin samples was observed. CONCLUSIONS: We suppose that nC60 treatment shifts immune response from Th2 to Th1 and restores to some extent the function of the skin barrier. This approach can be a good alternative to the treatment of allergic and other inflammatory diseases.

Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis.

Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD.

Small interfering RNAs targeted to interleukin-4 and respiratory syncytial virus reduce airway inflammation in a mouse model of virus-induced asthma exacerbation.

Asthma exacerbations are caused primarily by viral infections. Antisense and small interfering RNA (siRNA) technologies have gained attention as potential antiasthma and antiviral approaches. In this study we analyzed whether gene silencing of interleukin (IL)-4 expression and respiratory syncytial virus (RSV) replication by RNA interference is able to suppress allergen- and virus-induced responses in a mouse model of virus-induced asthma exacerbation. Knockdown efficacy of IL-4 siRNA molecules was analyzed in the human HEK293T cell line by cotransfection of six different siRNAs with a plasmid carrying mouse IL-4. The most potent siRNA was then used in a mouse model of RSV-induced asthma exacerbation. BALB/c mice were sensitized intraperitoneally with ovalbumin (OVA) and then infected 12 days later intranasally with RSV Long strain (1×10(6) TCID50/mouse), followed 1 day later by intranasal challenge with OVA for 3 days. Mice were pretreated intranasally three times with either siRNA to IL-4 or GFP control, 2 days before, and on the first two OVA challenge days. siRNAs to RSV or rhinovirus control were inoculated intranasally once, 3 hr before RSV infection. Combined anti-IL-4 and anti-RSV siRNAs were able to significantly reduce total cell counts and eosinophilia in bronchoalveolar lavage fluid, development of airway hyperresponsiveness, and airway inflammation and to downregulate IL-4 mRNA expression and RSV viral RNA, but to upregulate IFN-γ levels in lung tissues. We conclude that anti-helper T cells type 2 and antiviral siRNAs may constitute a new therapeutic approach for treatment of virus induced asthma exacerbations.