A randomized controlled trial of interleukin-1 receptor antagonist in a rabbit model of ascending infection in pregnancy.
OBJECTIVE
To determine whether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amniotic fluid concentrations of tumor necrosis factor alpha (TNF-alpha) and prostaglandins or clinical or microbiological outcomes in a model of ascending bacterial infection in pregnancy.


METHODS
Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation of the cervices with 10(6) - 10(7) cfu Escherichia coli. Animals were randomly assigned in a blinded manner to a 5-h intravenous infusion of human IL1-ra (10 mg/kg) or placebo beginning 1-2 h after inoculation. Blood was drawn from the does for assay of serum IL1-ra concentration before inoculation, at mid-infusion, after the infusion ended and at necropsy. At necropsy, temperature and cultures were taken, and aspirated amniotic fluid was pooled for assays of TNF-aalpha, prostaglandin E2 (PGE2) and ILI-ra.


RESULTS
Serum IL1-ra concentrations rose to a mean of 2 microg/ml at mid-infusion and fell markedly after the infusion to concentrations barely detectable at necropsy. Between the two groups, there were no significant differences in the rates of fever or positive cultures or in amniotic fluid concentrations of PGE2 or TNF-alpha. One unique finding was the demonstration that administration of human IL1-ra to the does resulted in measurable concentrations of human IL1-ra in the amniotic fluid.


CONCLUSIONS
Treatment with an intravenous infusion of human IL1-ra after cervical inoculation with E. coli did not affect clinical or microbiological outcomes or amniotic fluid concentrations of TNF-alpha or PGE2. This experiment providesthefirstdemonstration of passage of human IL1-ra from the maternal bloodstream to the amniotic fluid.
McDuffie
R S
RS
Department of Obstetrics and Gynecology, Kaiser Permanente, Denver, CO 80205, USA.
Davies
J K
JK
Leslie
K K
KK
Lee
S
S
Sherman
M P
MP
Gibbs
R S
RS
D000653:Amniotic Fluid / Q000737:chemistry / Q000276:immunology; D000818:Animals; D001831:Body Temperature; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000254:growth & development* / Q000276:immunology; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D011817:Rabbits; D011897:Random Allocation; D017472:Receptors, Interleukin-1 / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000276:immunology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone