Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis

Background: Chronic atopic dermatitis (AD) lesions are associated with colo nization by exotoxin-producing Staphylococcus aureus. Evidence suggests tha t cytokine production in AD, particularly of GM-CSF, prolongs survival of b oth peripheral blood monocytes and dermal monocyte-macrophages, the predomi nate inflammatory cell in lesions caused by chronic AD. Objective: We sought to determine whether the staphylococcal exotoxin, toxi c shock syndrome toxin-l (TSST-1), could stimulate prosurvival cytokine pro duction in monocytes and thereby inhibit apoptosis. Methods: Cultures of peripheral blood monocytes from normal donors and subj ects with AD were incubated with various concentrations of TSST-1, and the incidence of apoptosis was assessed by examining cytospin preparations and the appearance of hypodiploid DNA in the flow cytometer, Culture supernatan ts mere analyzed for GM-CSF, IL-1 beta, and TNF-alpha by ELISA, Results: TSST-1, in a concentration-dependent manner starting at 0.1 pg/mL, significantly inhibited monocyte apoptosis and resulted in the production of the prosurvival cytokines GM-CSF, IL-1 beta, and TNF-alpha. In coculture conditions with conditioned media from TSST-1-stimulatcd monocytes, with o r without neutralizing antibody to the various cytokines, the data show GM- CSF production was responsible for the inhibition of apoptosis, Conclusions: The data strongly suggest that staphylococcal exotoxins known to colonize skin lesions on patients with chronic AD may induce the product ion of GM-CSF, resulting in inhibition of monocyte-macrophage apoptosis, an d thereby contribute to the chronicity of this inflammatory disease.