FK506: therapeutic effects on lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr mice

Abstract

The effects of FK506, a new immunosuppressive agent, on the development of lupus dermatoses were investigated in the autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mouse, which is an animal model for the spontaneous development of skin lesions similar to those of human lupus erythematosus (LE). FK506 reduced the incidence of skin lesions, lupus nephritis, the titre of serum anti-double-stranded DNA antibodies and the massive T cell proliferation. The incidence and magnitude of IgG deposition at the dermoepidermal junction were not changed. These results suggest that FK506 is a promising immunosuppressive agent for the control of autoimmune skin diseases.

Short- and long-term effects of T-cell modulating agents in experimental autoimmunity

“…This is in accordance with the T-cell dependency of ANoA induction by Hg (Hultman et al, 1995), and the ability of calcineurin inhibitors to suppress activation and clonal expression of T-cells (Dumont, 2000). Our findings also tally with the ability of CyA (Gunn, 1983, Jones andHarris, 1985) and tacrolimus (Yamamoto et al, 1990, Furukawa et al, 1995 to prevent development of autoantibodies in murine lupus. However, we extend previous observations by showing that CyA inhibits induction of autoantibodies by Hg for not only 5 weeks (Aten et al, 1988), but for at least 19 weeks after stopping treatment.…”

“…HD tacrolimus inhibited and CyA suppressed the induction of tissue IC deposits by Hg, which is in accordance with observations in spontaneous rodent lupus nephritis for CyA (Lillevang et al, 1992) and tacrolimus (Yamamoto et al, 1990, Furukawa et al, 1995. Treatment with CyA for 3 weeks also inhibited development of tissue IC deposits during the following 19 weeks treatment with only Hg.…”

The Use of Topical Tacrolimus (FK506/Protopic) in Cutaneous Manifestations of Autoimmune Diseases

“…2,3 Furthermore, the intraperitoneal administration of tacrolimus has been found to be effective in reducing the incidence of skin lesions in the MRL/lpr mouse model of SLE. 8 Finally, a case series of 3 patients with severe, refractory SLE has reported showing a benefit of oral tacrolimus in two of the three patients in controlling manifestations of the disease, including vasculitis. 10 To date, there has been only 1 other small case series, but no clinical trials, involving the use of topical tacrolimus to treat the cutaneous manifestations of lupus.…”

“…7 The only adverse events reported were local irritation, pruritis, erythema, and burning, most of which tended to occur only when initiating treatment. 8 Furthermore, in a clinical trial of topical tacrolimus conducted in 180 children 7-16 years of age with atopic dermatitis, no systemic side effects were observed. 5 Other applications of topical tacrolimus to treat autoimmune skin diseases have been reported, including its successful use in the therapy for erosive mucosal lichen planus.…”

Tacrolimus in Dermatology

“…34 Furthermore, combining tacrolimus (2 mg/kg intraperitonally, three times weekly) with cyclophosphamide (20 mg/kg once monthly) may increase its efficacy. 35…”