A comparison of the stimulatory effects of cytokines on normal and psoriatic keratinocytes in vitro

Keratinocytes from normal and psoriatic skin were tested for their in vitro proliferative response to a range of concentrations of rIL-6, rTGF, rIL-8 and rGM-CSF using a serum-free culture system. With one exception, all normal cultures (11/12) were stimulated by 1000 ng/ml IL-6 (P<0.001). Six out of ten psoriatic keratinocyte cultures were also stimulated at this concetration, but this just failed to reach significance (P=0.05). As a group, the response by psoriatic keratinocytes to IL-6 was significantly less than that of normal keratinocytes (P=0.02). TGF at 1 ng/ml induced proliferation in approximately 60% of both normal (8/12,P<0.05) and psoriatic (6/10,P<0.1) keratinocyte cultures; there was no significant difference between the responses of the two groups to this cytokine. In addition, small numbers of both normal and psoriatic cultures responded to TGF over a concentration range of 0.1 to 100 ng/ml. Approximately half of the normal and psoriatic cultures were stimulated by 10–1000 ng/ml IL-8. However, the effect was not significant for the group at any of the concentrations tested. GM-CSF had minimal to no effect on most of the normal and psoriatic cultures tested. This study showed that psoriatic keratinocytes are equally responsive to the stimulatory effects of TGF and IL-8, but are less susceptible to IL-6 compared to keratinocytes from normal skin. These findings are consistent with a role for these cytokines in the maintenance of a hyperproliferative epidermis in psoriasis.