Unique alterations in infection-induced immune activation during pregnancy.
BACKGROUND
Immune responses to infection are uniquely regulated during gestation to allow for antimicrobial defence and tissue repair, whilst preventing damage to developing fetal organs or the triggering of preterm labour.


OBJECTIVE
A review and analysis of studies delineating gestation-specific immune modulation and intra-amniotic regulation of pro-inflammatory immunity.


METHODS
Identification of the alterations between the fetus/neonate and adult with regard to the endogenous and infection-induced expression of molecules with immune regulatory properties, and the characterisation of intra-amniotic immune mediators that inhibit bacterial-induced pro-inflammatory cytokine production.


METHODS
English and non-English publications from 1985 to the present.


METHODS
An electronic literature search using MEDLINE, PubMed, articles cited in the primary sources, as well as pregnancy-related immunology research from our laboratory at Weill Medical College of Cornell University.


RESULTS
During fetal development, interleukin (IL)-23, IL-10 and IL-6, as well as T-helper-17 (Th17)-mediated immune responses, are upregulated, whereas tumour necrosis factor-α (TNF-α) and IL-1β- and Th1-mediated immune responses are downregulated in the intrauterine environment (both the fetal compartment and the amniotic compartment). Infection-related immunity during gestation is preferentially directed towards combating extracellular microbial pathogens. Amniotic fluid and the neonatal circulation contain multiple components that improve the ability of the developing neonate to tolerate microbial-induced immune activation.


CONCLUSIONS
The repertoire of immune mechanisms to control infection and inflammation differ between fetal and adult life. The dual mechanisms of resistance to infection and tolerance to infection-induced immune activation prevent damage to the developing fetus and the triggering of premature labour.
Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, New York, NY 10065, USA. switkin@med.cornell.edu
S S
SS
Witkin
I M
IM
Linhares
A M
AM
Bongiovanni
C
C
Herway
D
D
Skupski
D000241:Adenosine / Q000502:physiology; D000328:Adult; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D055354:Exosomes / Q000502:physiology; D005260:Female; D005333:Fetus / Q000276:immunology*; D018260:Gelsolin / Q000502:physiology; D006657:Histones / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid / Q000502:physiology; D007111:Immunity, Cellular / Q000502:physiology*; D007155:Immunologic Factors / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D007752:Obstetric Labor, Premature / Q000276:immunology* / Q000382:microbiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D015854:Up-Regulation
D016207:Cytokines; D018260:Gelsolin; D006657:Histones; D007155:Immunologic Factors; D006820:Hyaluronic Acid; D000241:Adenosine