IL-8, IL-12 and IL-10 cytokines generation by neutrophils, fibroblasts and neutrophils- fibroblasts interaction in psoriasis
ABSTRACT Psoriasis is a common skin disease affecting about 1-3% of the world population. Many types of cells, including lymphocytes, dendritics APCs (antigen presenting cells), NKT (natural killer T) cells, neutrophils, keratinocytes and fibroblasts are involved in the pathogenesis of psoriasis.The aim of our study was to assess in psoriatic patients the production of IL-8, IL-10 and IL-12 cytokines by neutrophils, fibroblasts and fibroblasts - neutrophils interaction.
The production of IL-8, IL-10 and IL-12 cytokines was evaluated in supernatants after cells incubation for 21 h in culture medium alone and in medium in the presence of IL-8 or TNF-α. Concentrations of IL-8, IL-10, IL-12 were measured by enzyme-linked immunosorbent assay (ELISA) method using commercially available kits.
Our results demonstrate that fibroblasts are not able to produce IL-10 and IL-12 but they generate IL-8. The amount of IL-8 depends on the site of derivation of fibroblasts and on the stimuli. Neutrophils released IL-8, IL-12 (at a lower level in psoriatic patients) and IL-10 but only in the case of healthy donors and at a very low concentration. Moreover, we observed higher concentrations of IL-12 and IL-8 in supernatants as a result of fibroblasts-neutrophils interaction in psoriatic patients.
Our results suggest that fibroblasts take part in the inflammatory reaction in psoriasis via cytokines or direct interaction with neutrophils. Fibroblasts probably do not exert any anti-inflammatory effect.
SourceAvailable from: Patricia Hernandez[Show abstract] [Hide abstract]
ABSTRACT: Psoriasis is a chronic inflammatory disease with a prevalence of approximately 2-3% in the general population. The majority of diagnosed patients have plaque psoriasis, and about 20% have moderate-to-severe disease. Itolizumab, a new monoclonal antibody specific for the CD6 molecule mainly expressed on T lymphocytes, has demonstrated to inhibit in vitro ligand-induced proliferation and pro-inflammatory cytokine production. We assessed the immunological and histopathological effect of the antibody using clinical samples taken from 26 patients with moderate-to-severe psoriasis included in a clinical trial. The precursor frequency of lymphocytes activated with anti-CD2/CD3/CD28 beads, as well as the number of interferon (IFN)-γ-secreting T cells after stimulation, were measured at different time points of the study. Serum cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. Additionally, lymphocyte infiltration and epidermis hyperplasia were studied in five patients. A significant reduction in T cell proliferation capacity and number of IFN-γ-producing T cells was found in treated patients. Serum levels of interleukin-6, tumor necrosis factor and IFN-γ showed an overall trend toward reduction. No anti-idiotypic antibody response was detected. A significant reduction in the epidermis hyperplasia was observed in analyzed patients. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.mAbs 03/2014; 6(3). DOI:10.4161/mabs.28376 · 4.73 Impact Factor
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