1. ¹Signum Biosciences, Monmouth Junction, New Jersey, USA
2. ²Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA
3. ³Department of Chemistry, Princeton University, Princeton, New Jersey, USA

Correspondence: Maxwell B. Stock, 1 Deer Park Drive suite L2, Monmouth Junction, New Jersey 08852, USA. E-mail: mstock@signumbio.com

Received 11 November 2006; Revised 11 June 2007; Accepted 13 July 2007; Published online 20 September 2007.

Abstract

N-Acetyl-S-farnesyl-L-cysteine (AFC), a modulator of G protein and G-protein coupled receptor signaling, inhibits neutrophil chemotaxis and other inflammatory responses in cell-based assays. Here, we show topical AFC inhibits in vivo acute inflammation induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and arachidonic acid using the mouse ear model of inflammation. AFC inhibits edema, as measured by ear weight, and also inhibits neutrophil infiltration as assayed by direct counting in histological sections and by measuring myeloperoxidase (MPO) activity as a neutrophil marker. In addition, AFC inhibits in vivo allergic contact dermatitis in a mouse model utilizing sensitization followed by a subsequent challenge with 2,4-dinitrofluorobenzene. Unlike the established anti-inflammatories dexamethasone and indomethacin, AFC's action was restricted to the site of application. In this mouse model, both dexamethasone and indomethacin inhibited TPA-induced edema and MPO activity in the vehicle-treated, contralateral ear. AFC showed no contralateral ear inhibition for either of these end points. A marginally significant decrease due to AFC treatment was seen in TPA-induced epidermal hyperplasia at 24 hours. This was much less than the 90% inhibition of neutrophil infiltration, suggesting that AFC does not act by directly inhibiting protein kinase C.