CD1a expression in psoriatic skin following treatment with propylthiouracil, an antithyroid thioureylene

Abstract

BackgroundThe antithyroid thioureylenes, propylthiouracil (PTU) and methimazole (MMI), are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells). Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque.MethodsBiopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU) daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied.ResultsDespite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment.ConclusionsIt appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells.

Comparative study of histopathological and immunohistochemical findings in skin biopsies from patients with psoriasis before and after treatment with acitretin

“…Furthermore, various non‐retinoid drugs have shown to promote similar outcomes in epidermal thickness, 26,29–33,39 epidermal inflammation, 29,32,39 CK10 positivity, 7,34 CK16 positivity 27,29,30,33,39 and Ki67 positivity 7,29,30,32,34,39 . However, there are only two studies comparing the amount of Langerhans’ cells in epidermis before and after anti‐psoriatic treatment using CD1a as marker 32,35 . Whereas the present study showed decrease in number of CD1a‐positive cells after treatment with acitretin, that result being similar to what Asadullah et al 32 found with systemic IL‐10 therapy, Elias et al 35 did not notice any difference after treatment with propylthiouracil.…”

“…There are many studies comparing histological and immunohistochemical aspects of psoriasis before and after treatment with several drugs 7,26–36 . However, there are three studying psoriasis before and after retinoid therapy under the same scope 16,23,37 among which only one has acitretin as one of the elected drug 16 …”

Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks

“…Psoriasis is an autoimmune‐mediated disease where T cells activated by mature Langerhans cells play a pivotal role in the pathogenesis of the disease. Histopathological key phenomena in the psoriatic plaque are accumulation of T‐cell subsets and epidermal hyperproliferation with premature keratinization 10–12 . In the present study, however, immunoreactivity of makers of differentiation (involucrin) and proliferation (Ki‐67) did not differ significantly between the treatment modalities, indicating that at 6 weeks both treatments do not appear to be substantially different in influencing the differentiation and proliferation status of psoriasis.…”

Expression of IL‐1Rrp2 by human myelomonocytic cells is unique to DCs and facilitates DC maturation by IL‐1F8 and IL‐1F9

“…However, taken together with our current study, these studies may also show a pleiotropic effect of IL-1Rrp2 and its ligands on different cells and it is not known what the effect of these cytokines have on Langerhans cells or epidermal DCs in the skin, which are phenotypically similar to MDDCs [21,22]. One study has shown that Langerhans cells act to dampen skin inflammation [29] and another study has shown that Langerhans cell recruitment is increased in the skin of psoriatic patients successfully treated with propylthiouracil, which has anti-inflammatory properties [30]. The potential of IL-1 cytokines for immunomodulatory therapies has previously been reviewed by Dumont [31].…”