The natural interleukin-1 receptor antagonist prevents interleukin-1-induced preterm delivery in mice.
OBJECTIVE
Interleukin-1 has been implicated in the mechanisms responsible for preterm parturition in the setting of intrauterine infection. This cytokine is produced by human decidua, stimulates prostaglandin production by intrauterine tissues, and induces preterm parturition in mice. The purpose of this study was to determine whether pretreatment with the natural interleukin-1 receptor antagonist can block interleukin-1-induced preterm parturition in mice.


METHODS
Balb/CJ female mice impregnated by B6D2 F-1 male mice were randomly allocated to one of the following treatment groups: (1) saline solution (n = 15), (2) human recombinant interleukin-1 alpha or human recombinant interleukin-1 beta (n = 12), (3) human recombinant interleukin-1 receptor antagonist (n = 13), and (4) human recombinant interleukin-1 receptor antagonist plus human recombinant interleukin-1 (n = 24).


RESULTS
An interleukin-1 dose of 10 micrograms per mouse induced preterm parturition in all cases. Pretreatment with interleukin-1 receptor antagonist (dose 1 mg per animal) prevented interleukin-1-induced preterm parturition. Interleukin-1 receptor antagonist administration was not associated with demonstrable side effects including behavioral changes, vaginal bleeding, duration of pregnancy, and pregnancy outcome.


CONCLUSIONS
Our results suggest that interleukin-1-induced preterm delivery in mice is mediated by the interleukin-1 receptor.
Romero
R
R
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201.
Tartakovsky
B
B
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D051379:Mice; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000517:prevention & control*; D011247:Pregnancy; D012795:Sialoglycoproteins / Q000494:pharmacology*
C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins