An Altered Response by Psoriatic Keratinocytes to Gamma Interferon

To determine whether psoriatic keratinocytes differ from normal keratinocytes in their response to gamma interferon, epidermal cell suspensions from normal and from lesional and uninvolved psoriatic skin were cultured in the presence of gamma interferon and the induction of HLA-DR expression and inhibition of cell growth were measured. The addition of 10(2) units of gamma interferon/ml during a 7-day culture period significantly increased mean HLA-DR+ cell numbers in 21 epidermal suspensions of normal from 3.9 to 24.1% (P less than 0.0001), uninvolved psoriatic from 8.4 to 33.1% (P less than 0.0001), and to a lesser extent lesional psoriatic biopsies from 12.6 to 18.3% (P less than 0.01). However, the increase in HLA-DR+ cell numbers in these latter cultures was significantly less than that observed in either normal or uninvolved psoriatic epidermal cell cultures (P less than 0.0001). Furthermore, 3H]thymidine incorporation was substantially decreased by gamma interferon in 16 out of 22 (73%) cultures of normal epidermal cells; this decrease was statistically significant (P less than 0.01). In contrast, only 4 out of 11 (36%) lesional and 9 out of 21 (43%) uninvolved psoriatic epidermal cultures showed comparable inhibition of proliferation. These findings suggest that psoriatic keratinocytes have an altered response to gamma interferon; this could explain the infrequency of keratinocyte HLA-DR expression in psoriatic plaques in vivo and may also contribute to the increased epidermal proliferation that characterizes this disease.