Retinoids are used in the treatment of inflammatory
skin diseases and
malignancies, but studies characterizing the in vivo actions of these drugs in humans are lacking.
Isotretinoin is a
pro-drug for
all-trans retinoic acid, which can induce long-term remissions of
acne; however, its complete mechanism of action is unknown. We hypothesized that
isotretinoin induces remission of
acne by normalizing the innate immune response to the commensal bacterium Propionibacterium acnes. Compared with normal subjects, peripheral blood monocytes from
acne patients expressed significantly higher levels of
Toll-like receptor 2 (TLR-2) and exhibited significantly greater induction of TLR-2 expression following P. acnes stimulation. Treatment of patients with
isotretinoin significantly decreased monocyte TLR-2 expression and subsequent inflammatory
cytokine response to P. acnes after 1 week of
therapy. This effect was sustained 6 months following cessation of
therapy, indicating that TLR-2 modulation may be involved in the durable therapeutic response to
isotretinoin. This study demonstrates that
isotretinoin exerts immunomodulatory effects in patients and sheds light on a potential mechanism for its long-term effects on
acne. The modulation of TLR-2 expression on monocytes has important implications in other inflammatory disorders characterized by TLR-2 dysregulation.