Figure 1

Evidence for a defective TNF/IL-10 axis in IL-10 knockout and TNF^ARE mutant mice. (A) Weight distribution and (B) cumulative percent survival of Il-10^-/- Tnf^-/- and control mice. (C) Representative photomicrographs (200) of the proximal colon of Il-10^-/- Tnf^-/- from: (i) 8-week-old Il-10^-/- Tnf^+/- control mice showing prominent transmural inflammation (arrows), epithelial cell hyperplasia and goblet cell loss; (ii) 14-week-old Il-10^-/- Tnf^-/- colon showing normal epithelial integrity; (iii) 12-week-old Il-10^-/- Tnf^-/- asymptomatic mouse showing mild signs of submucosal inflammation (asterisk); (iv) 12-week-old Il-10^-/- Tnf^-/- diseased mouse showing severe inflammation. (D) Kinetics of TNF protein accumulation (upper) and production per hour (lower) in Il-10^+/+ and Il-10^-/- TEPM following LPS stimulation in vitro. TNF and IL-10 protein levels in collected supernatants were determined by ELISA. Results shown as mean SD values from five cultures/group. (E) Kinetics of TNF and IL-10 protein production in Tnf^+/+ (closed circles) and Tnf^ARE/+ (open circles) mice following LPS challenge in vivo. Mice were challenged with 100 g/ml LPS intraperitoneally and subsequently exsanguinated via cardiac puncture at the indicated time points. TNF and IL-10 protein levels in sera were determined by ELISA. Results shown as mean SD values from four mice/time point. (F) Kinetics of TNF and IL-10 in Tnf^+/+ (closed circles) and Tnf^ARE/+ (open circles) TEPM and following LPS stimulation, in vitro. TEPM were cultured as before and subsequently stimulated with LPS (1 g/ml) for 12 h.