CX-659S ((S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione), a newly discovered anti-inflammatory compound, exerts inhibitory effects against
picryl chloride-,
oxazolone-, and
dinitrochlorobenzene-induced acute
contact hypersensitivity responses (CHRs) characterized by Th1-type reactions. Furthermore, this compound suppressed chronic CHRs characterized by Th2-type reactions, which is well known to mimic many, if not all, events occurring within the lesional skin of patients with
atopic dermatitis (AD). The present study was conducted to determine the combined effect of topical
CX-659S with topical
corticosteroid on immediate type (ITR), late type (LTR), and delayed type
hypersensitivity (DTHR)
allergic reactions that are involved in AD. An ineffective dose of
CX-659S (0.03 mg/ear) combined with
betamethasone valerate (BV) significantly potentiated inhibitory activity of BV alone (0.1 micro g/ear and 0.3Shizuokag/ear) on both the ITR and the LTR in mice with the
ovalbumin (OVA)-induced biphasic cutaneous reaction. Furthermore, the combined effect of
CX-659S with BV was also observed on
dinitrochlorobenzene (
DNCB)-induced DTHR in guinea pigs. These results indicate that
CX-659S has a combined effect with
corticosteroids on every ITR, LTR, and DTHR. Proper treatment with
corticosteroids for a safe and effective treatment of AD is needed. Thus, the combination
therapy of topical
CX-659S with topical
corticosteroid would be one of the potential approaches for devising a proper treatment with
corticosteroids.