Anti-tumor necrosis factor alpha F(ab')2 antibody fragments protect in murine polymicrobial sepsis: concentration and early intervention are fundamental to the outcome.
BACKGROUND
Negative results are frequent using anti-TNFalpha antibodies in sepsis models and clinical trials.


RESULTS
Different prophylactic doses of anti-TNFalpha 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-TNFalpha 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.
Márquez-Velasco
R
R
Department of Immunology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No 1, Col. Sección XVI, D. F. CP 14080, Tlalpan, México.
Bojalil
R
R
Buelna
A
A
Flores-Guzmán
F
F
Estevez-Ramirez
J
J
Laguna
J
J
Hernández
A M
AM
Díaz-Quiñonez
A
A
Paniagua-Solís
J F
JF
D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D016207:Cytokines / Q000097:blood; D004926:Escherichia coli / Q000302:isolation & purification; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D018805:Sepsis / Q000517:prevention & control*; D013210:Staphylococcus / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D016207:Cytokines; D007140:Immunoglobulin Fab Fragments; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha