Mast cells in psoriatic skin are strongly positive for interferon-gamma

The increased number and early activation of cutaneous mast cells is a typi cal feature of psoriatic inflammation. Interferon-gamma (IFN-gamma) is beli eved to be one of the important mediators in the cytokine cascade of psoria sis. Human mast cells have been previously reported to release various cyto kines upon stimulation including interleukin (IL) -4, IL-5, IL-6, IL-8, IL- 13 and tumour necrosis factor-alpha. Here we report that human mast cells s ynthesize also IFN-gamma at mRNA and protein level and that the number of I FN-gamma producing mast cells is significantly increased in the psoriatic s kin. IFN-gamma immunoreactivity in mast cells was demonstrated by staining non-lesional and lesional skin sections from 21 patients with psoriasis. Te n patients with atopic dermatitis (AD) and five healthy persons served as c ontrol groups. The percentage (mean +/- SD) of IFN-gamma + mast cells in le sional compared with non-lesional psoriatic skin was 67 +/- 18% vs. 44 +/- 17% (P < 0.0001, paired t-test), respectively, but only 9 +/- 6% vs. 10 +/- 7% in corresponding skin samples of AD. In the skin of healthy controls, o nly 12 +/- 12% of the mast cells were IFN-gamma +. Using immunoelectron mic roscopy, we confirmed the ultrastructural localization of IFN-gamma within the granules of mast cells in psoriatic skin. In addition, stimulation of a human mast cell line HMC-1 with phorbol myristate acetate (PMA) (100 nmol/ L) for periods of 2-24 h induced expression of IFN-gamma mRNA, which peaked at 24 h. When HMC-1 cells were stimulated with PMA (100 nmol/L) for period s of 0-3 days, the cells released IFN-gamma protein, peaking on day 1. Thes e results provide further evidence for the important role of mast cells in the pathogenesis of psoriasis.