Prednisolone blunts early vascular and monocyte responses to intradermal LPS, but not neutrophil recruitment.

Toll-like receptor 4 (TLR4)-mediated inflammation in human skin is often studied via intradermal lipopolysaccharide (LPS). While previous models showed strong immune activation, they lacked early time-point data, limiting understanding of initial inflammatory kinetics. Corticosteroids like prednisolone are known anti-inflammatories, but their impact on very early immune events, particularly neutrophil recruitment, remained unclear. This study aimed to fill this gap by characterizing initial responses and prednisolone's effects.

This randomized, placebo-controlled, double-blind trial involved 36 healthy male volunteers. Participants received oral prednisolone or placebo (1:1) for 2.5 days before intradermal LPS challenge (5 ng/injection) on the volar forearm. Responses were monitored at 1, 3, 6, and 24 hours. Vascular changes were assessed using multispectral imaging and laser speckle contrast imaging. Immune responses, including cytokine levels, were measured via suction blister fluid analysis, flow cytometry, and immunohistochemistry of skin punch biopsies.

Intradermal LPS rapidly increased skin perfusion and erythema, detectable from 1 hour. IL-8 peaked at 1 hour, while IL-6 and IL-1β peaked at 3-6 hours. A significant neutrophil influx and NET formation began as early as 1 hour, with NET formation peaking at 24 hours. Classical monocyte infiltration followed neutrophil recruitment. NLRP3 inflammasome activation, indicated by ASC and NLRP3 expression, peaked at 3 hours.

Prednisolone significantly reduced vascular responses and infiltration of intermediate monocytes. However, prednisolone had a limited effect on early neutrophil recruitment and NET formation, consistent with prior observations.