Anti-tumor necrosis factor α F(ab')₂ antibody fragments protect in murine polymicrobial sepsis: Concentration and early intervention are fundamental to the outcome

Abstract.

Background

Negative results are frequent using anti-TNFα antibodies in sepsis models and clinical trials.

Methods and Results

Different prophylactic doses of anti-TNFα F(ab')₂ antibody fragments were compared for the prevention of death by sepsis induced by cecal ligation and puncture (CLP) in mice. High (10 mg/kg) and very low (0.01 and 0.1 mg/kg) concentrations of anti-TNFα antibody fragments were not the most adequate for treating polymicrobial sepsis, since they did not significantly improve survival. To the contrary, intermediate doses (1 mg/kg) significantly protected the challenged animals. Protective activity was also observed when administration of the antibody fragments was initiated early (up to 30 min) after CLP.

Conclusions

These results suggest that in processes where excessive production of cytokines is involved, the aim should be to return them to their physiologically acting range but not to inhibit their production. The timing of initiating therapy should also be considered in order to maximize the possible benefits.