Fig. 6: Energy metabolism during acute and chronic cutaneous DTHR.

a Simplified illustration of the tricarboxylic acid (TCA) cycle with additional information of amino acid entry as anaplerotic (black frame, grey background) and cataplerotic substrates. Dashed line for indirect reactions with multiple steps. b Metabolite normalised concentration changes (in arbitrary unit (a.u.)) illustrated as box plots with max. to min. whisker, individual replicate points and median within the inflamed ears during acute 4 h (medium grey, upward triangle), 24 h (light grey, downward triangle) and chronic 0 h (bright yellow, dot), 4 h (dark yellow, dot), 12 h (orange, dot) and 24 h (brown, dot) cutaneous DTHR (compared to naive control (dark grey, square), P value ****<0.0001, ***<0.001, **<0.01, *<0.05, n = 5 animals, except A 24 h n = 4 animals). Statistical significance test stars shown for comparisons to naive control by one-way ANOVA. The ear swelling response during the acute cutaneous DTHR peak at 24 h is illustrated by the orange arrow, and the chronic cutaneous DTHR peak at 4 h is illustrated by the blue arrow. The dashed lines show a non-significant trend.