Figure 7.

Inhibition of p38 MAP kinase prevents toxin A–induced enteritis in mouse ileum. The p38 inhibitor SB203580 or SB202474, a control compound inactive on p38 kinase activity (100 μg/loop), was injected into the lumen of an ileal loop as described in Methods. After 30 minutes, toxin A (10 μg) was administered, and animals were sacrificed 4 hours later. Loops were cut out and fluid secretion was assessed by measuring the weight/length ratio (mg/cm). Enteritis severity was measured by histology, using scores to quantify neutrophil infiltration, congestion, and villus destruction. (a, b) SB203580 inhibited toxin A–induced fluid secretion by 74% (a) (P < 0.001) and reduced enteritis severity by 78% (P = 0.005) (b), whereas the inactive analog SB202474 had no significant effect (means and SE are shown; 9–10 loops per group). (c–f) Histological features of toxin A–induced enteritis and their inhibition by SB203580. (c) Control ileum. (d) Toxin A alone causing destruction of villous architecture, neutrophil infiltration, edema, and ulceration. (e) SB203580 pretreatment preserved villous integrity, prevented neutrophil infiltration and ulceration, and partially inhibited edema. (f) SB202474 pretreatment was not protective.