The intradermal LPS challenge in healthy volunteers has proven to be a valuable tool to study local inflammation in vivo. In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challenge for future investigational drugs.

24 healthy male volunteers received a two-and-a-half- day BID pre-treatment with topical clobetasol propionate 0.05% and six healthy volunteers received a two-and-a-half- day BID pre-treatment with oral prednisolone at 0.25 mg/kg bodyweight per administration. Subjects received one injection regimen of either 0, 2 or 4 intradermal LPS injections (5 ng LPS in 50 µL 0.9% NaCL solution). The LPS response was evaluated by non-invasive (perfusion, skin temperature, and erythema) and invasive assessments (cellular and cytokine responses) in suction blister exudate.

Both corticosteroids significantly suppressed the clinical inflammatory response (erythema p = 0.0001 for clobetasol and p = 0.0016 for prednisolone; heat p = 0.0245 for clobetasol, perfusion p < 0.0001 for clobetasol and p = 0.0036 for prednisolone). Clobetasol also significantly reduced the number of monocytes subsets, dendritic cells, NK cells and T cells in blister exudate. A similar effect was observed for prednisolone. No relevant corticosteroid effects were observed on the cytokine response to LPS.

We successfully demonstrated that the anti-inflammatory effects of corticosteroids can be detected using our intradermal LPS challenge model, validating it for evaluation of future investigational drugs, as initial assessment of the anti-inflammatory effects of such compounds in a minimally invasive manner.