The single greatest cause of mortality and morbidity in newborn infants is premature birth. Although the pathogenic factors responsible for preterm parturition are unknown, recent studies indicate that endotoxin from bacterial infection can provoke the release of tumor necrosis factor (TNFalpha), interleukin 1 (IL-1beta), and platelet activating factor (PAF) from the decidua and are then projected to cause premature labor through some unknown mechanism. We propose to test two hypotheses: that TNFalpha, IL-1beta and PAF directly alter myometrial contractile function and that endotoxemia alters uterine contractile characteristics. Contractile effects of TNFalpha, IL-1beta and PAF will be examined singly and in combination with known agonists in uterine effects of TNFalpha, PAF and IL-1beta are altered by known receptor antagonists, determine if gestational age alters susceptibility to TNFalpha, PAF and/or IL-1beta, and determine the role of the decidua in mediating the effects of these substances on myometrial contractile mechanisms. E. coli endotoxemia will be induced to determine E. coli endotoxemia alters contractile responses of pregnant uterus to TNFalpha, IL-1beta, oxytocin and PGF2alpha, and to determine if endotoxin is necessary to """"""""prime"""""""" the gravid uterus and/or its decidua for expression of the myometrial effects of TNFalpha, and IL-1beta. These studies are designed to provide insight into cellular mechanisms responsible for the relationship of bacterial infection to premature labor. An understanding of these mechanisms could lead to the development of methods that would reduce premature births, as well as to a better comprehension of basic physiologic mechanisms that govern uterine function and parturition.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Physician Scientist Award (K11)
Project #
1K11HD000947-01
Application #
3087084
Study Section
Maternal and Child Health Research Committee (HDMC)
Project Start
1991-06-01
Project End
1996-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211