Somatostatin, dendritic cells and peptide T in psoriasis : a clinical, immunohistochemical and functional study

Peptide T is an octapeptide designed to block the CD4 receptor. In a phase 1 study 9 psoriasis patients were treated with 2 mg peptide T i.v. once daily for 28 days and followed for a further 3 months. Five patients improved their PASI score >50%. The clinical results were confirmed by assessments of the histopathological score and epidermal thickness on biopsies. Peptide T treatment caused an increase in CD1-positive dendritic cells and a decrease in infiltrating lymphocytes. Immunohistochemical analysis revealed major changes in a population of somatostatin-immunoreactive dendritic cells during the treatment. Somatostatin is a neuropeptide that inhibits the release of several hormones. It also affects fundamental lymphocyte functions, such as proliferation and antibody production, and somatostatin has been used in several studies of psoriasis. We found more somatostatin- immunoreactive cells in psoriasis lesions than in normal skin. These cells did not co-express CD1a, CD35, CD45RB, CD45RO, CD68, factor XIIIa or S-100, and they probably represent a specific population of dendritic cells. A subgroup co-expressed HLA-DR, which suggests that these cells can present antigens to T-cells. Changes in somatostatin- and factor XIIIa-immunoreactive dendritic cells in psoriatic skin were then studied in biopsies taken during treatment with clobetasol propionate or calcipotriol. We found a significant reduction in the number of somatostatin- and factor XIIIa-positive cells after both treatments. The rate of reduction in the somatostatin-positive cells differed between the groups and closely paralleled healing. Most somatostatin-positive cells in psoriasis are found in the dermis. In view of the known effects of somatostatin on the immune system, these cells may regulate the function of surrounding lymphocytes. Somatostatin exerts its effects by binding to five distinct receptors (SSTR1-5). We used RT-PCR to map the mRNA expression of these receptors in normal blood T-lymphocytes and in eight leukemic T-cell lines. Normal T-cells, but not the leukemic T- cells, expressed mRNA for SSTR1 and SSTR 5. SSTR2, 3 and 4 were present in all the T-cells examined. SSTR5 was selectively expressed in activated normal T-cells. Normal T-lymphocytes and all the T-cell lines were negative with respect to somatostatin mRNA expression. Thus, although T-cells can respond to somatostatin, they do not seem to produce somatostatin themselves. A prerequisite for the localization of T-lympho