Bidirectional concentration-dependent effects of tumor necrosis factor alpha in Shigella dysenteriae-related seizures

Abstract

We have previously demonstrated that pretreatment of mice with Shigella dysenteriae sonicate enhanced their susceptibility to pentylenetetrazole-induced seizures and that tumor necrosis factor alpha (TNF-alpha) was proconvulsive in this respect. The present study shows that TNF-alpha, at high concentrations, may also exert a suppressive effect on Shigella-mediated seizures. This implies that high levels of TNF-alpha may play a protective role in neurologic complications of S. dysenteriae infection.

FIG. 1.

Effect of pretreatment with different doses of S. dysenteriae 60R sonicate (60R) on PTZ-induced seizures. Data are presented as means ± standard errors of the means. (A) Mice treated 7 h before PTZ. P = 0.013 for saline (n = 36) versus 1 LD₅₀ (n = 23), P = 0.008 for saline versus 2 LD₅₀ (n = 36), P = 0.05 for saline versus 4 LD₅₀ (n = 24), and P = 0.22 for saline versus 8 LD₅₀ (n = 21). (B) Mice treated 24 h before PTZ. P = 0.003 for saline versus 60R at 1 LD₅₀ (n = 12), P = 0.001 for saline versus 60R at 2 LD₅₀ (n = 23), P = 0.046 for saline versus 60R at 4 LD₅₀ (n = 15), and P = 0.196 for saline versus 60R at 8 LD₅₀ (n = 15).

FIG. 2.

Serum TNF-α production in response to different doses of S. dysenteriae 60R sonicate (60R). The values are the means of determinations from five animals ± standard errors (R² = 0.75, P = 0.05).

FIG. 3.

Enhancement of PTZ-induced seizures by anti-mTNF-α in mice pretreated with a high dose of S. dysenteriae 60R sonicate (60R). PTZ (50 mg/ml) was given i.p. at 24 h. P = 0.09 for 60R (n = 24) versus saline (n = 26), P = 0.054 for 60R versus 60R with anti-mTNF-α (n = 26), and P = 0.048 for 60R with anti-mTNF-α versus saline.

FIG. 4.

Effect of exogenous TNF-α on the enhancement of PTZ-induced seizures by S. dysenteriae 60R sonicate (60R). (A) Mice pretreated with S. dysenteriae 60R sonicate 7 h before PTZ. P = 0.04 for 60R versus saline, and P = 0.003 for 60R versus 60R followed by TNF-α. n = 12 in all groups. (B) Mice pretreated with S. dysenteriae 60R sonicate 24 h before PTZ. P = 0.003 for 60R versus saline, and P = 0.002 for 60R versus 60R followed by TNF-α. n = 12 in all groups.