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.
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Received 2 January 2006; returned for revision 12 March 2006; accepted by G. Wallace 3 April 2006
R. Márquez-Velasco, recipient of a PhD scholarship by Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico. Doctorado en Ciencias Biológicas, Universidad Autónoma Metropolitana-Iztapalapa
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Márquez-Velasco, R., Bojalil, R., Buelna, A. et al. Anti-tumor necrosis factor α F(ab')2 antibody fragments protect in murine polymicrobial sepsis: Concentration and early intervention are fundamental to the outcome. Inflamm. res. 55, 378–384 (2006). https://doi.org/10.1007/s00011-006-6001-6
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DOI: https://doi.org/10.1007/s00011-006-6001-6