Biological drugs targeting
tumor necrosis factor-α, such as
infliximab, are highly effective in
psoriasis. The interference with keratinocyte apoptosis has been included among the possible effects of
infliximab in
psoriasis, although the available data are still controversial. The purpose of our study was to verify the action of
infliximab on psoriatic keratinocytes. Keratinocyte apoptosis was evaluated in the lesional psoriatic skin of 11 patients at baseline and a different time point during treatment with
infliximab.
Infliximab (5 mg/kg) was given intravenously at weeks 0, 2, and 6, followed by maintenance infusions every 8 weeks. Pretreatment with intravenous
hydrocortisone was performed prior to each infusion. Keratinocytes with apoptotic features were histologically identified according to the following changes:
chromatin condensation at the periphery of the nucleus, cytoplasmic vesiculation, nuclear fragmentation, nuclear pyknosis. Immunohistochemical assessment of p53 and
caspase-3 expression was also performed. At baseline, prior to treatment with
infliximab, lesional epidermis showed 1.2-3.2% p53-positive apoptotic keratinocytes in the basal zone. The number of p53-positive apoptotic keratinocytes increased
after treatment with
infliximab, already at day 1-2 after the first infusion, and such cells were localized at basal and suprabasal layers or were through all layers. There was no immunoreactivity for
caspase-3 at any time point examined. Our results suggest that induction of p53-related keratinocyte apoptosis might be one of the mechanisms of
infliximab action in
psoriasis.