Diet‐induced dermatitis response of hairless rats to systemic treatment with cyclosporin A (Sandimmun®), cyclosporin H and FK506

Abstract

Weaned hairless rats were fed a diet deficient in fat, magnesium and folacin. After approximately 1 week, an erythematous dermatitis developed which was associated with extreme generalized pruritus. Scratching led to excoriations and hemorrhagic crusting. The acute stage (pruritic rash) resolved after several days and was followed by sporadic non-itching relapses. Subsequent to the onset of symptoms, rats were treated orally, once daily for 3 days with CyA, CyH or FK506. The immunosuppressants CyA and FK506 caused a dose-dependent inhibition of symptoms in contrast to CyH. The immediate clinical response was associated with changes in blood histamine, white blood cell counts and histological parameters. Since CyH is known to lack immunosuppressive activity, these results may indicate that the cutaneous changes induced by the nutritional deficiency are associated with immunological abnormalities. The results may also indicate mechanisms influenced by CyA and FK506 but not by CyH; for example, release of chemical mediators from inflammatory cells.

The hypomagnesic rat model: dermatitis‐prone hairless rats with mild magnesium depletion fed a diet low in lipids did not develop pruritic dermatitis

“…Rats in the diet group were fed a diet 20 times lower in lipids, while the magnesium content was five times lower. Magnesium in the control diet in our experiment matched control diets in other reports (3, 8). Consequently, serum Mg 2+ was lower in the diet group as compared with the control group.…”

“…The mechanism(s) by which hypomagnesaemia in hairless rats can lead to eczematous skin lesions may involve mediators in the lipid metabolism, presumably leukotriene B 4 (4, 5). The dermatitis can be relieved by giving magnesium to the rats (6, 7), by antagonising the leukotriene B 4 receptor (4) and by suppressing the immune system (8, 9). Lipids in the magnesium deficient diet may be important since the condition is postulated to be aggravated by also depleting lipids in the diet so that the diet is low both in magnesium and lipids (MND) diet (8).…”

In vivo Pharmacological Disease Models for Psoriasis and Atopic Dermatitis in Drug Discovery*

“…Disease models that comprise many of the features that are characteristic of atopic dermatitis include hapten‐induced dermatitis in mice, NC/Nga mice, and genetically engineered mouse models. Other relevant disease models in drug discovery that have been included in relation to atopic dermatitis are the magnesium deficient induced dermatitis‐model in rats (Bavandi et al 1992), superantigen induced dermatitis in hairless guinea pigs (Petersen et al 2003a), and passive cutaneous anaphylaxis in mice (Inagaki et al 1984).…”

Atopic Dermatitis and Asthma: Parallels in the Evolution of Treatment

“…50,[52][53][54][55][56][57] In both short-term (12-week double-blind) and long-term (12-month open-label) clinical studies, topical tacrolimus has been shown to be an effective and safe for AD treatment in children and adults. 50,56 Longer term safety data (2-3 years) for AD treatment in patients 2 to 15 years of age have been reported.…”