Elidel
Corticosteroids but not pimecrolimus affect viability, maturation and immune function of murine epidermal Langerhans cells.

Hoetzenecker W, Meingassner JG, Ecker R, Stingl G, Stuetz A, Elbe-Burger A.

DIAID, Department of Dermatology, Medical University of Vienna, Austria.

Given the importance of dendritic cells in the immune response, we investigated the effect of corticosteroids (CS) on the integrity, survival, and function of murine Langerhans cells (LC) in comparison with pimecrolimus, a novel anti-inflammatory drug for the topical treatment of atopic dermatitis. BALB/c mice were treated twice on one day with ethanolic solutions of the compounds. At 24-72 h after the last application, we observed fragmented DNA, caspase-3 activity, and an upregulation of CD95 expression in LC from mice treated with CS but not in LC of pimecrolimus- or vehicle-treated animals. CS-epidermal cell (EC) supernatants but not pimecrolimus-EC supernatants contained significantly lower amounts of soluble factors (GM-CSF, TNF-alpha, IL-1alpha) required for LC survival and maturation than EC supernatants from vehicle-treated mice. With regard to LC maturation, CS but not pimecrolimus inhibited the expression of CD25, CD205, and costimulatory molecules. In line with this, LC from pimecrolimus-treated mice were similar to LC from vehicle-treated mice in their capacity to stimulate antigen-presenting function and migration, whereas LC from CS-treated mice were greatly impaired in these abilities. In summary, our data show for the first time that CS but not pimecrolimus induce apoptosis in LC in situ, implying that the prolonged use of CS could have adverse effects on the skin immune system.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15086553&dopt=Abstract pimecrolimus Elidel



Elidel
Determination of the effect of calcineurin inhibitors on the rat's immune system after KLH immunisation.

Roman D, Ulrich P, Paul G, Court M, Vit P, Kehren J, Mahl A.

Novartis Pharma AG, Preclinical Safety, Basel, Switzerland. danielle.roman pharma.novartis.com

The calcineurin inhibitors cyclosporin A (CsA), tacrolimus (FK506) and pimecrolimus (ASM981) are on the market for the oral treatment of psoriasis and atopic dermatitis and topical treatment of atopic dermatitis, respectively. The effect of these treatments on the immune response was investigated in this study after immunisation of rats with keyhole limpet hemocyanin (KLH). Male rats (10 per group) were orally administered pimecrolimus at 10 or 30 mg/kg/day), tacrolimus at 3 mg/kg/day or CsA at 20 mg/kg/day for 4 weeks. Control animals similarly received the vehicle only. The last five animals per group were immunised and challenged with KLH on days 16 and 24, respectively. Eight days after the last injection, the immune function was investigated by detecting KLH-specific antibodies in the serum and by examination of cell infiltration at the site of the KLH-challenge. In addition, a correlation between functional and structural changes was established by quantification of lymphocyte sub-populations in the blood or residing in lymphatic tissue. In KLH-immunised rats, CsA caused complete suppression of the KLH-specific IgM and IgG production, whereas only IgG production was affected by pimecrolimus at 30 mg/kg/day and more so by tacrolimus at 3 mg/kg/day. Immunophenotyping of lymphocyte sub-populations in spleen and lymph node indicated a decrease in T lymphocytes with pimecrolimus at 30 mg/kg/day, tacrolimus and CsA, whereas these changes were marginal for pimecrolimus at 10 mg/kg/day. Immunophenotyping of peripheral white blood cells (WBC) revealed a decrease in the absolute number of T lymphocytes with all three test items. In comparison with non-immunised animals, a slight increase in absolute numbers of T lymphocytes was observed in KLH-immunised animals treated with pimecrolimus at 10 or 30 mg/kg/day. In conclusion, the ability of the immune system to respond to KLH was not affected by pimecrolimus at 10 mg/kg/day whereas a decrease in immune function was noted in the other groups as follows: pimecrolimus (30 mg/kg/day) < tacrolimus (3 mg/kg/day) < CsA (20 mg/kg/day).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15093258&dopt=Abstract pimecrolimus Elidel



Elidel
Pimecrolimus 1% cream for cutaneous lupus erythematosus.

Kreuter A, Gambichler T, Breuckmann F, Pawlak FM, Stucker M, Bader A, Altmeyer P, Freitag M.

Department of Dermatology and Allergology, Ruhr-University Bochum, Germany.

Topical treatment of cutaneous lupus erythematosus usually includes potent glucocorticosteroids. However, prolonged use causes adverse side effects including skin atrophy as the foremost concern. In contrast to glucocorticosteroids, the anti-inflammatory and immunosuppressive macrolactam pimecrolimus has no atrophogenic potential. Affected areas of 11 patients with different forms of lupus erythematosus were treated with pimecrolimus 1% cream under semiocclusive conditions twice daily for 3 weeks. Skin involvement before and after therapy was assessed by means of a clinical score. In all patients, significant regression of skin lesions was observed after therapy (P <.001). This was an open and uncontrolled study on a limited number of cases. We suggest that pimecrolimus 1% cream could be an efficacious and safe treatment option for cutaneous lupus erythematosus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15337984&dopt=Abstract pimecrolimus Elidel



Elidel
The use of topical tacrolimus and pimecrolimus to treat psoriasis: a review.

Scheinfeld N.

Department of Dermatology, St Lukes Roosevelt Hospital, New York NY, USA. Scheinfeld earthlink.net

Tacrolimus ointment and pimecrolimus cream are approved in the United States for treatment of atopic dermatitis. Tacrolimus and pimecrolimus are both calcineurin inhibitors and function as immunosuppressants. Their mechanisms have been discussed elsewhere. This article will discuss their utility in treating psoriasis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15347485&dopt=Abstract pimecrolimus Elidel