Hideki Kitagaki

Psychological stress with long-standing allergic dermatitis causes psychodermatological conditions in mice.

Psychological factors have long been assumed to be involved in the pathogenesis of allergic skin diseases. The effects of psychological stress on allergic contact dermatitis (ACD) have been experimentally well investigated; however, the effects of ACD on stress responses are largely unknown. Here, we report that preceding chronic ACD dramatically affects the behavioral and physiological stress responses to social isolation (a psychological stressor). In male BALB/c mice, social isolation combined with long-standing (>2 months) ACD by repeated hapten application caused characteristic symptoms, including chronic dermatitis from persistent self-scratching, behavioral changes related to fear/anxiety, and elevated serum IgE levels. The symptoms were maintained by social isolation alone without further hapten application after the onset, and were improved by resocialization. Treatment with topical corticosteroids exacerbated chronic scratch dermatitis, whereas it was effective for chronic ACD. These results show that the symptoms represent a de novo development of a specific disease state and not a mere exacerbation of a preexisting allergic inflammation. With this experimental protocol, similar results were obtained in several other strains of mice. This murine model provides a tool for investigating the pathogenesis and treatment of allergic skin disease with psychodermatological aspects.

Effects of Carteolol Hydrochloride on the In Vitro Production of LPS-Induced Proinflammatory Cytokines by Murine Macrophage

We investigated whether carteolol hydrochloride, which has intrinsic sympathomimetic activity (ISA), inhibits the production of proinflammatory cytokines using mouse macrophages (MPs) and peripheral-blood mononuclear cells (PBMCs). MPs and PBMCs were collected from BALB/C strain mice, treated simultaneously with lipopolysaccharide (LPS) and test agents (carteolol hydrochloride, timolol maleate, betaxolol hydrochloride, levobunolol hydrochloride, or nipradilol) in medium, and incubated in a CO2 incubator. TNF-alpha and IL-6 in medium were measured by ELISA. Carteolol hydrochloride significantly inhibited the production of TNF-alpha and IL-6 by MPs at 10(-5) M and higher (p < 0.01) or PBMCs at 10(-6) M and higher (p < 0.01) compared to the controls, while the other test agents had no inhibitory effect. Carteolol hydrochloride inhibited the production of proinflammatory cytokines by inflammatory cells, raising the possibility that this intraocular hypotensive drug may be expected to have anti-inflammatory effects in patients with increased intraocular tension and postoperative inflammation.