TY - JOUR
T1 - Prospective association of maternal immune pro-inflammatory responsivity and regulation in pregnancy with length of gestation
AU - Gyllenhammer, Lauren E.
AU - Entringer, Sonja
AU - Buss, Claudia
AU - Simhan, Hyagriv N.
AU - Grobman, William A.
AU - Adam, Emma K.
AU - Keenan-Devlin, Lauren Slubowski
AU - Borders, Ann E.
AU - Wadhwa, Pathik D.
N1 - Funding Information:
Funding for this study was provided by NIH HHSN275201200007I‐‐HHSN27500005. The preparation of this paper was additionally supported by NIH grants R01 MD‐010738, R01 AG‐050455 and K99/R00 HD097302. The authors have no conflicts of interest to report.
Funding Information:
Funding for this study was provided by NIH HHSN275201200007I--HHSN27500005. The preparation of this paper was additionally supported by NIH grants R01 MD-010738, R01 AG-050455 and K99/R00 HD097302. The authors have no conflicts of interest to report.
Publisher Copyright:
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2021/5
Y1 - 2021/5
N2 - Problem: The immune system represents a leading pathway of interest in the pathophysiology of preterm birth. The majority of human clinical studies interrogating this pathway have utilized circulating immune biomarkers; however, these concentrations typically reflect only basal production but not key functional properties of the immune system, particularly variation in the pro-inflammatory response to antigen challenge and the regulation of this response. Thus, in this study, we utilized an ex vivo stimulation protocol that quantifies these processes, and we examined their prospective association with the gestation length and risk of preterm birth. Method of Study: Immune responsiveness and regulation were assessed in 128 pregnant women in mid-gestation using an ex vivo stimulation protocol. Maternal pro-inflammatory responsivity of leukocytes was quantified by assessing the release of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β in response to antigen stimulation, and regulation of the pro-inflammatory response was quantified by assessing the suppression of stimulated cytokine response upon co-incubation with increasing dexamethasone concentrations (ie, glucocorticoid receptor resistance; GRR). Results: Higher maternal GRR, indicating impaired regulation of the pro-inflammatory response, was significantly and independently associated with shorter gestational length (β = −0.42, p =.0091) and a 3.0-fold increase in risk for preterm birth (OR = 3.01, 95% CI = 1.17–7.70, p =.0218). Basal circulating IL-6 and TNF-α were not associated with either outcome. Conclusion: The association of maternal GRR with length of gestation and preterm birth risk suggests that the processes represented by this measure—maternal pro-inflammatory propensity and immune regulation—may provide further mechanistic insight into the pathophysiology of preterm birth.
AB - Problem: The immune system represents a leading pathway of interest in the pathophysiology of preterm birth. The majority of human clinical studies interrogating this pathway have utilized circulating immune biomarkers; however, these concentrations typically reflect only basal production but not key functional properties of the immune system, particularly variation in the pro-inflammatory response to antigen challenge and the regulation of this response. Thus, in this study, we utilized an ex vivo stimulation protocol that quantifies these processes, and we examined their prospective association with the gestation length and risk of preterm birth. Method of Study: Immune responsiveness and regulation were assessed in 128 pregnant women in mid-gestation using an ex vivo stimulation protocol. Maternal pro-inflammatory responsivity of leukocytes was quantified by assessing the release of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β in response to antigen stimulation, and regulation of the pro-inflammatory response was quantified by assessing the suppression of stimulated cytokine response upon co-incubation with increasing dexamethasone concentrations (ie, glucocorticoid receptor resistance; GRR). Results: Higher maternal GRR, indicating impaired regulation of the pro-inflammatory response, was significantly and independently associated with shorter gestational length (β = −0.42, p =.0091) and a 3.0-fold increase in risk for preterm birth (OR = 3.01, 95% CI = 1.17–7.70, p =.0218). Basal circulating IL-6 and TNF-α were not associated with either outcome. Conclusion: The association of maternal GRR with length of gestation and preterm birth risk suggests that the processes represented by this measure—maternal pro-inflammatory propensity and immune regulation—may provide further mechanistic insight into the pathophysiology of preterm birth.
KW - cortisol
KW - glucocorticoid resistance
KW - inflammation
KW - interleukin-1 beta
KW - interleukin-6
KW - length of gestation
KW - preterm birth
KW - tumor necrosis factor
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U2 - 10.1111/aji.13366
DO - 10.1111/aji.13366
M3 - Article
C2 - 33099840
AN - SCOPUS:85096689432
SN - 1046-7408
VL - 85
JO - American Journal of Reproductive Immunology
JF - American Journal of Reproductive Immunology
IS - 5
M1 - e13366
ER -