Effect of a human immunoglobulin preparation for intravenous use in a rabbit model of meningococcal endotoxin-induced shock.
METHODS
Endotoxin shock is mediated by various cytokines, including tumor necrosis factor. Treatment of patients with i.v. immunoglobulin has been shown to reduce the concentration of circulating cytokines. The purpose of this study was to determine the protective effects of immunoglobulin for i.v. use on meningococcal endotoxin-induced shock in a rabbit model. Experimental animals were challenged with i.v. meningococcal endotoxin (lipo-oligosaccharide) 10 micrograms/kg, and treated with either a 2-hr i.v. immunoglobulin infusion (400 mg/kg) or a similar saline infusion that was initiated 30 mins before endotoxin challenge. Control animals were challenged with saline alone.


RESULTS
Compared with untreated control animals, pulse rate increased (p less than .007) and mean arterial pressure and serum bicarbonate concentrations decreased (p less than .02) in both experimental groups, but did not differ between immunoglobulin-treated and saline-treated animals (p greater than .05) at any time after the endotoxin challenge. Geometric mean serum endotoxin concentrations were significantly (p less than .03) lower in the immunoglobulin-treated animals at 60, 120, 180, 240, 300, and 360 mins after the endotoxin challenge. The geometric mean serum tumor necrosis factor level at 1 hr after the endotoxin challenge in the immunoglobulin-treated experimental animals was lower than in saline-treated animals (5.53 vs. 8.47 tumor necrosis factor enzyme-linked immunosorbent assay U/mL), but not significantly so (p greater than .05). Mortality rate was similar in both experimental groups; eight (67%) of 12 saline-treated experimental rabbits and seven (70%) of ten immunoglobulin-treated rabbits died. All untreated control animals survived 24 hrs.


CONCLUSIONS
In this model of circulatory shock in rabbits, i.v. immunoglobulin: a) does not significantly alter the physiologic responses to endotoxin challenge; b) significantly reduces endotoxin concentrations; c) reduces tumor necrosis factor concentrations, but not significantly; and d) does not improve survival rate.
Saladino
R
R
Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115.
Baldwin
G
G
Alpert
G
G
Parsonnet
J
J
Gillis
Z
Z
Thompson
C
C
Siber
G
G
Fleisher
G
G
D000704:Analysis of Variance; D000818:Animals; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004731:Endotoxins / Q000097:blood / Q000633:toxicity; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008297:Male; D009345:Neisseria meningitidis; D011817:Rabbits; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004731:Endotoxins; D016756:Immunoglobulins, Intravenous; D014409:Tumor Necrosis Factor-alpha