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.