Atopic dermatitis (AD) usually develops in patients with an individual or family history of allergic diseases, and is characterized by chronic relapsing inflammation seen especially in childhood, association with IgE hyperproduction and precipitation by environmental factors. However, the exact etiology of AD has been unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is required. We found that skin lesions, which were clinically and histologically very similar to human AD, spontaneously appeared on the face, neck, ears and dorsal skin of inbred NC/Nga mice when they were raised in non-sterile (conventional) circumstances, but not under specific pathogen-free conditions. Plasma levels of total IgE in conventional NC/Nga mice were markedly elevated from 8 weeks of age, correlating with clinical skin severity of dermatitis. Immunohistochemical examination of the skin lesion showed increased numbers of mast cells and CD4+ T cells containing IL-4 necessary for IgE synthesis. Thus, NC/Nga mice suffered from dermatitis very similar to human AD with IgE hyperproduction, which may be triggered by some environmental factor(s).

The ability of the anti‐allergic drugs, sodium cromoglycate (SCG), lodoxamide, traxanox, RU31156 and the β‐adrenoceptor agonist sulbutamol to inhibit IgE‐dependent histamine and prostaglandin D2 (PGD2) release was assessed using human dispersed lung mast cells. The anti‐allergic drugs were weak inhibitors of histamine release, high concentrations (100–1000 μm) producing < 35% inhibition. Salbutamol produced 39% inhibition at 10 μm. The efficacy of both SCG and salbutamol was inversely related to the concentration of anti‐IgE used for challenge and to the degree of histamine release. Rapid tachyphylaxis was observed with all anti‐allergic drugs but not with salbutamol. Cross‐tachyphylaxis was observed between SCG and the other anti‐allergic drugs, suggesting a common mechanism of action. No cross‐tachyphylaxis was observed between SCG and salbutamol. SCG was significantly (P < 0.001) more effective in inhibiting PGD2 than it was histamine release. Preferential inhibition of PGD2 compared with histamine release was less marked (P < 0.05) with salbutamol and not significant with the other anti‐allergic drugs. Mast cells dispersed by enzymatic digestion of human lung released more histamine on immunological challenge than mechanically dispersed cells obtained by fine chopping of tissue. Enzyme treatment of mechanically dispersed cells removed this difference. Enzymatically and mechanically dispersed cells responded similarly to the inhibitory effects of SCG and salbutamol. Our results suggest that salbutamol is a more effective inhibitor of mediator release from human lung mast cells than anti‐allergic drugs. However, with the low levels of mediator release achieved during an allergic reaction in man in vivo, both salbutamol and SCG are likely to be effective inhibitors of both preformed and newly generated mediators.

The effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga (NC) mice was examined. FK506 ointment (0.1-1%) suppressed the development of dermatitis and was also therapeutically effective against established dermatitis. Increases in CD4-positive T cells (helper T cells), mast cells, eosinophils and immunostaining of interleukin (IL)-4, IL-5 and IgE were confirmed in the skin of the NC mice, and FK506 ointment suppressed all of these changes. Increased plasma IgE was also confirmed in the NC mice, and treatment with FK506 ointment reduced the plasma IgE level. These results suggested that FK506 suppressed the dermatitis by inhibiting the activation of inflammatory cells and by blocking the cytokine network in the skin of the NC mice. The commercially available steroid ointments showed only marginal effect on the development of dermatitis and showed some signs of side effects such as alopecia or atrophy of the skin. The effect of the steroids might have been masked by these side effects because the steroids showed similar inhibitory effects on the skin histopathological changes and the increase of plasma IgE. From these results, FK506 ointment can be expected to be a useful drug for atopic dermatitis.

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