GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR CONTRIBUTES TO ENHANCED MONOCYTE SURVIVAL IN CHRONIC ATOPIC-DERMATITIS

Evidence suggesting that prolonged effector cell survival may contribu te to perpetuation of inflammation prompted us to ask whether monocyte macrophages, the predominate inflammatory cell in the lesion of chron ic atopic dermatitis (AD), exhibit enhanced survival in AD. Cultures o f peripheral blood monocytes from patients with chronic AD, psoriasis, and from normal (NL) donors were examined for morphologic features an d DNA fragmentation characteristic of cells undergoing the process of apoptosis (programmed cell death). Cultures of AD monocytes exhibited a significantly lower incidence of apoptosis than did cultures of NL m onocytes (45 vs 68%, P < 0.01), or psoriatic monocytes (45 vs 80%, P < 0.01). Furthermore, AD monocytes were unresponsive to both IL-1, an i nhibitor of apoptosis, and IL-4, an enhancer of apoptosis, in comparis on to cultured NL monocytes. Of note, GM-CSF in a concentration-depend ent fashion, decreased the incidence of apoptosis in NL monocyte cultu res and rendered them unresponsive to these cytokines. These findings suggested that GM-CSF may enhance monocyte survival in AD. In support of this hypothesis, AD monocyte cultures produced fivefold more GM-CSF than did cultures of NL monocytes or psoriatic monocytes (P < 0.05). Additionally, there was a significantly greater number of GM-CSF mRNA expressing cells detected by in situ hybridization in biopsies of lesi ons of chronic AD than in acute AD or NL skin (P < 0.05). Finally, NL monocytes incubated with supernatants obtained from monocytes of AD pa tients exhibited significant inhibition of apoptosis, an effect that c ould be ablated by a neutralizing antibody to GM-CSF. Taken together, these data strongly suggest that increased production of GM-CSF by cel ls from patients with AD inhibits monocyte apoptosis and may contribut e to the chronicity of this inflammatory disease.