Anti-tumor necrosis factor a F(ab') 2 antibody fragments protect in murine polymicrobial sepsis: Concentration and early intervention are fundamental to the outcome
Por:
Márquez-Velasco R., Bojalil R., Buelna A., Flores-Guzmán F., Estevez-Ramirez J., Laguna J., Hernández A.M., Díaz-Quiñonez A., Paniagua-Solís J.F.
Publicada:
1 ene 2006
Resumen:
Background: Negative results are frequent using anti-TNF? antibodies in sepsis models and clinical trials. Methods and Results: Different prophylactic doses of anti-TNF? 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-TNF? 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. © Birkhäuser Verlag, 2006.
Filiaciones:
Márquez-Velasco R.:
Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No 1, Col. Secc. XVI, D. F. CP 14080, Tlalpan, Mexico
Bojalil R.:
Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No 1, Col. Secc. XVI, D. F. CP 14080, Tlalpan, Mexico
Department of Health Care, Universidad Autónoma Metropolitana-Xochimilco, México, D. F., Mexico
Buelna A.:
Dirección de Investigación en Inmunotecnología, Laboratorios Silanes S.A. de C.V./Instituto Bioclon, S.A. de C.V., México, Mexico
Flores-Guzmán F.:
Dirección de Investigación en Inmunotecnología, Laboratorios Silanes S.A. de C.V./Instituto Bioclon, S.A. de C.V., México, Mexico
Estevez-Ramirez J.:
Dirección de Investigación en Inmunotecnología, Laboratorios Silanes S.A. de C.V./Instituto Bioclon, S.A. de C.V., México, Mexico
Laguna J.:
Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No 1, Col. Secc. XVI, D. F. CP 14080, Tlalpan, Mexico
Hernández A.M.:
Departments of Infectology and Microbiology, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, Mexico
Díaz-Quiñonez A.:
Dirección de Investigación en Inmunotecnología, Laboratorios Silanes S.A. de C.V./Instituto Bioclon, S.A. de C.V., México, Mexico
Paniagua-Solís J.F.:
Dirección de Investigación en Inmunotecnología, Laboratorios Silanes S.A. de C.V./Instituto Bioclon, S.A. de C.V., México, Mexico
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