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


METHODS
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.


CONCLUSIONS
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.
Hirsch
Emmet
E
Department of Obstetrics, Evanston Northwestern Healthcare, Evanston, IL 60201, USA. e-hirsch@northwestern.edu
Filipovich
Yana
Y
Mahendroo
Mala
M
D000818:Animals; D020070:Cervical Ripening / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004927:Escherichia coli Infections / Q000150:complications* / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009215:Myometrium / Q000201:enzymology; D007752:Obstetric Labor, Premature / Q000382:microbiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2