Figure 5.

Nec-1 and Nec-1i show a paradoxical dose response in TNF-induced SIRS. (a) Effect of Nec-1 and Nec-1i on TNF shock-associated hypothermia. DMSO, Nec-1 or Nec-1i were injected i.v. at a dose of 6 mg/kg b.w. 17 min before challenge with 10 μg mTNF i.v. (about LD₁₀₀); Nec-1 and Nec-1i were equipotent in protection. (b) Survival curve for the experiment described in a. (c) TNF shock-associated hypothermia for different doses of Nec-1 and Nec-1i. Both compounds were injected at different doses with the same regimen as above, before injection with 7.5 μg mTNF (about LD₅₀). Hi: 6 mg/kg b.w; Mo: 3 mg/kg b.w; and Lo: 0.6 mg/kg b.w. Nec-1 and Nec-1i paradoxically sensitized mice to TNF-induced SIRS. (d) Survival curve for different doses of Nec-1 and Nec-1i. (e) Levels of damage-associated markers detected in the plasma of mice treated as indicated with TNF and different doses of Nec-1 and Nec-1i. A cumulative result of two independent experiments is represented (a–d). Number of mice is indicated between brackets. ^*P<0.05, ^**P<0.001 and ^***P<0.0001