Signaling via the type I IL-1 and TNF receptors is necessary for bacterially induced preterm labor in a murine model

Am J Obstet Gynecol. 2006 May;194(5):1334-40. doi: 10.1016/j.ajog.2005.11.004. Epub 2006 Apr 21.


Objective: We have shown previously that interleukin 1 (IL-1) signaling is not necessary for bacterially induced preterm delivery in mice. We now test whether combined signaling of IL-1 and tumor necrosis factor (TNF) is critical for this process.

Study design: Female mice lacking the type I receptors for IL-1 and TNF (Il1r1/Tnfrsf1a double-knockouts) and normal controls underwent intrauterine inoculation with killed Escherichia coli bacteria on day 14.5 of a 19- to 20-day gestation. Preterm delivery rates within 48 hours were recorded and gene expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR).

Results: Il1r1/Tnfrsf1a double-knockout mice had significantly lower rates of preterm delivery than controls (8% vs 69% with 7 x 10(7) bacteria, P = .002, and 52% vs 81% with 1.4 x 10(8) bacteria, P = .003) and significantly lower myometrial levels of cyclooxygenase (COX)-2, but not COX-1 mRNA. There were no genotype- or treatment-related differences in cervicovaginal and lower uterine expression of mRNAs for a variety of genes associated with cervical ripening.

Conclusion: The combination of IL-1 and TNF signaling plays a critical role in bacterially induced labor and myometrial COX-2 production in the mouse. Cervical gene expression patterns during bacterially induced preterm labor suggest fundamental differences from spontaneous term labor in the cervical ripening process.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cervical Ripening / genetics
  • Cyclooxygenase 2 / genetics
  • Escherichia coli Infections / complications*
  • Escherichia coli Infections / enzymology
  • Female
  • Gene Expression
  • Interleukin-1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myometrium / enzymology
  • Obstetric Labor, Premature / microbiology*
  • Pregnancy
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-1 / metabolism*
  • Receptors, Interleukin-1 Type I
  • Receptors, Tumor Necrosis Factor, Type I / metabolism*
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Interleukin-1
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Receptors, Interleukin-1 Type I
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • Cyclooxygenase 2