Birth Outcome can be Dependent on Balance of Pro- and Anti-inflammatory Cytokines

Andrew F. Olshan, Ph.D. and David A. Savitz, Ph.D.
University of North Carolina Chapel Hill
P30ES010126

Background: Cytokines are regulatory proteins produced by immune systems cells act as intercellular mediators in the generation of an immune response. Cytokines that stimulate inflammation are known as pro­inflammatory cytokines; those that inhibit it are logically known as anti­inflammatory cytokines. Anti­inflammatory cytokines are known to play a critical role in pregnancy maintenance. They are thought to protect the developing blastocyst by downregulating inflammatory and cytotoxic activity until the placental barrier is developed. Abnormal cytokine production favoring inflammation is thought to play a role in preterm birth either through increased pro­inflammatory cytokine or decreased anti­inflammatory cytokine production. To determine whether genetic variation in anti­inflammatory cytokines could influence a woman’s risk of adverse reproductive outcomes, this team of NIEHS­supported scientists examined the relationships of twelve genetic polymorphisms in five anti­inflammatory cytokines with spontaneous pre­term birth and births resulting in babies small­for­gestational age.

Advance: The results show that African­American women with a specific genetic polymorphism for interleukin­4 had about a 3­fold increase in the risk for spontaneous pre­term birth. In Caucasian women, carriers of the "low­producing" polymorphisms for interleukin­4 and interleukin­10 had markedly reduced risks for small­for­gestational age babies. Women of either race with the "high­producing" form of interleukin-­ had increased risks for small­for­gestational age babies.

Implications: These results are somewhat paradoxical in that decreased production of interleukin­4 caused both increased risk for spontaneous pre­term birth and decreased risk for babies small­for­gestational age. However, increased production of anti­inflammatory cytokines increased the risk of small­for­gestational age. These data suggest that maintaining the proper balance of pro­ and anti­inflammatory cytokines is crucial for good pregnancy outcomes and deviations in either direction may increase the likelihood of pre­term birth or low­birth weight babies.

Citation: Engel SA, Olshan AF, Savitz DA, Thorp J, Erichsen HC, Chanock SJ. Risk of small­for­gestational age is associated with common anti¨inflammatory cytokine polymorphisms. Epidemiology. 2005 Jul;16(4):478-86.