Mast cells in atopic dermatitis.

Tacrolimus-loaded ethosomes: physicochemical characterization and in vivo evaluation.

Background: Dyshidrotic palmoplantar eczema is a frequent disease often running a chronic relapsing course. Topical glucocorticosteroids form the mainstay of therapy, and alternatives are urgently warranted. Objective: This study was performed to compare the efficacy of tacrolimus (FK506) 0.1% ointment and mometasone furoate 0.1% ointment in the treatment of dyshidrotic palmoplantar eczema. Methods: Sixteen patients were included in the study after a randomized, observer-blind, intrapersonal comparison protocol. After a 2-week washout period, the active treatment phase amounted to 4 weeks with twice-daily topical application of test substances and additional use of emollients at will. Thereafter, patients were monitored at weekly intervals up to 8 weeks. Results: The dyshidrotic area and severity index showed a more than 50% reduction of baseline values after 2 weeks of active treatment both for FK506 ( P = .003) and mometasone furoate ( P = .022) in palmar areas. After active treatment, a nonsignificant increase in the dyshidrotic area and severity index was seen with FK506 treated areas. Fourteen of 16 patients had recurring symptoms requiring further therapy within 3 weeks after the active treatment phase. Conclusion: Treatment with FK506 offers the possibility for rotational therapy with mometasone furoate in long-standing cases of chronic dyshidrotic palmar eczema. (J Am Acad Dermatol 2002;46:73-7.)

https://www.jaad.org/article/S0190-9622(02)20678-7/pdf

Topical tacrolimus (FK506) and mometasone furoate in treatment of dyshidrotic palmar eczema: a randomized, observer-blinded trial.

Scratching behavior was induced in 12 strains of mice and the frequency was compared. An injection of histamine at a dose of 50 nmol induced frequent scratching behavior only in ICR mice, although the same dose of serotonin induced frequent scratching behavior in all strains of mice except for A/J. Histamine (10 nmol), serotonin (1 nmol), substance P (50 nmol) and passive cutaneous anaphylaxis induced significant vascular permeability increase in BALB/c, ICR, ddY and NC/Nga mice. These four stimuli also induced frequent scratching behavior in ICR mice. However, they failed to induce substantial increase in the incidence of scratching in the other three strains, except for ddY, which exhibited a slight but significant increase against substance P injection. These results suggest that the ICR mouse is a good responder for scratching behavior against various stimuli, especially against histamine. Thus ICR mice may be suitable for studying mediators and/or mechanisms for itching.

Scratching behavior in various strains of mice.

The newly developed immunomodulator tacrolimus (FK506) is the first of a new class of agents that have enormous potential to change the way that dermatoses are treated and managed. Tacrolimus has been found to be active in a topical formulation with the latter exerting its effects by acting on the signal transduction pathways inside T cells and inhibiting gene transcription. The result is decreased responsiveness of T cells to antigens. Percutaneous absorption of tacrolimus is higher in diseased skin as opposed to healthy skin and, therefore, the drug will be taken in at progressively lower quantities as lesions heal. There is limited systemic absorption of tacrolimus over the course of therapy. The most extensive experience with tacrolimus has been in treating atopic dermatitis. In numerous trials, tacrolimus ointment 0.03-0.3% has shown to be effective in reducing the symptoms and severity of atopic dermatitis in adults and the paediatric population. Furthermore, there have been no significant toxic effects associated with topical therapy with tacrolimus. The most common complaint is that of local irritation after applying the ointment. This is generally transient and the patient is able to continue with therapy. The other dermatoses where tacrolimus has been used include contact dermatitis, psoriasis and pyoderma gangrenosum.

Tacrolimus: a review of its use for the management of dermatoses

Production of IgE caused by repeated topical application of 2,4-dinitrofluorobenzene (DNFB) to the ears of BALB/c mice was investigated. Ear thickness increased in proportion to the number of applications. Eczematous changes of the skin included marked infiltration of neutrophils, eosinophils, and monocytes and hypertrophy of the epidermis. Ear thickness due to inflammation reached a maximum 24 hours after the second, third, fourth, and fifth applications. The strong expression of interferon-gamma and IL-2 messenger RNA (mRNA) in the skin lesions indicated the participation of Th1 type helper T cells in the delayed-type hypersensitivity reaction. After the fifth application, the mice showed an immediate cutaneous reaction in addition to the delayed-type hypersensitivity reaction. The immediate reaction appeared within 1 hour of application. Hapten-specific IgE also was detected in serum from the mice, and the expression of germline and productive Cepsilon mRNA was detected in cervical lymph nodes, whereas productive Cepsilon mRNA was detected in the spleen. These results indicate that five topical applications of DNFB to the ear produce local eczematous dermatitis and increase serum hapten-specific IgE level in mice. Eczematous dermatitis is mainly caused by Th1 type T cells, and IgE production is mediated by Th2 type T cells in the cervical lymph nodes. In addition, IgE class switching occurs in the cervical nodes and IgE production occurs in both lymph nodes and spleen.

Immunoglobulin E Production in Mice by Means of Contact Sensitization with a Simple Chemical, Hapten.

FK-506 and Cyclosporin A Potentiate the IgE Antibody Production by Contact Sensitization with Hapten in Mice.

Due to the inhibition of 5-lipoxygenase-activating protein (FLAP), BAY x1005 is a new selective inhibitor of leukotriene synthesis. The effects of BAY x1005 on the antigen- and bacterial lipopolysaccharide (LPS)-induced airway hyperresponsiveness in guinea pigs were investigated. Six times provocation of aeroantigen caused biphasic increases in airway resistance which peaked at 1 hr (immediate phase reaction) and 4 hrs (late phase reaction). It also caused airway hyperreactivity to acetylcholine. BAY x1005 at doses of 10 mg/kg and 30 mg/kg significantly inhibited antigen-induced increase in respiratory resistance (Rrs) at 1 and 4 hrs after the last antigen challenge. Simultaneously, BAY x1005 inhibited the antigen-induced airway hyperresponsiveness at doses of 10 and 30 mg/kg and airway eosinophilia (bronchoalveolar lavage study) at a dose of 30 mg/kg. In addition, BAY x1005 at a dose of 30 mg/kg inhibited bacterial LPS-induced airway hyperreactivity to acetylcholine. In this model, BAY x1005 did not affect the increase of the number of leukocytes in bronchoalveolar lavage fluid. These results suggest that BAY x1005 is a potent anti-asthmatic agent with an inhibitory action to airway hyperreactivity.

Effect of a novel leukotoriene synthesis inhibitor, BAY x1005,on antigen- and LPS-induced airway hyperresponsiveness in guinea pigs.

Effect of Prednisolone on IgE-dependent Biphasic Cutaneous Reaction in BALB/c Mice.

The effect of a novel thromboxane A2 receptor antagonist, BAY-u-3405, on experimental allergic airway and skin reactions was studied in vivo. At doses of 3-30 mg/kg BAY-u-3405 clearly inhibited the U-46619-induced increase in respiratory resistance (Rrs) in guinea pigs. BAY-u-3405 at doses of 3 and 30 mg/kg inhibited the aerosolized antigen-induced biphasic increase in respiratory resistance in guinea pigs. Moreover, BAY-u-3405 inhibited repeated aeroantigen-induced airway hyperactivity and airway inflammation in mice. In IgE antibody-mediated biphasic skin reactions in mice, both immediate and late-phase reactions were inhibited by 10 mg/kg of BAY-u-3405. These results demonstrate the efficacy of BAY-u-3405 on the antigen-induced late-phase reactions in the airway and skin in guinea pigs and mice, and antigen-induced airway hyperactivity in mice.

The effect of a thromboxane A_2 receptor antagonist BAY-u-3405 on experimental allergic reactions.

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