Etretinate has proven to be effective in the treatment of
psoriasis. Since abnormal proliferation and
cytokine secretion are well-known features of psoriatic epidermis, we studied the in vitro effects of
etretinate on these two processes using human keratinocytes.
Etretinate promoted proliferation of normal human keratinocytes (NHKs) grown in keratinocyte growth medium (KGM) but not in
growth factor-deficient keratinocyte basic medium (KBM). Moreover,
etretinate partly overcame growth inhibition by PMA.
Etretinate was shown to have an effect on either
IL-1 alpha or
IL-8 secretion in unstimulated NHKs. In HSC-1, a human
squamous cell carcinoma cell line cultured in 20% FCS/DMEM, inhibited
IL-1 alpha secretion and enhanced
IL-8 secretion. These results indicate that the effects of
etretinate on keratinocyte proliferation and
cytokine secretion may depend on cell type and culture conditions. Stimulation of NHKs with PMA significantly enhanced
IL-1 alpha and
IL-8 secretion, and these effects were inhibited by
etretinate. However,
etretinate failed to inhibit rTNF alpha-induced
IL-8 secretion, suggesting that
etretinate regulation of NHK
cytokine secretion may also depend on the stimulus. As treatment of keratinocytes or epidermis with PMA can induce
psoriasis-like changes, so might the experimental "anti-PMA" activity of
etretinate be related to its therapeutic benefit in the treatment of
psoriasis.