From the Guidelines
For studying preeclampsia and spontaneous preterm birth using maternal plasma in early pregnancy, the 12 most informative cytokines to evaluate would be IL-6, TNF-α, IL-1β, IL-8, IL-10, IL-4, IFN-γ, IL-17, VEGF, PlGF, sFlt-1, and MCP-1. These cytokines provide a comprehensive profile of inflammatory processes, immune regulation, and angiogenic factors critical in the pathophysiology of both conditions, as highlighted in recent research recommendations 1. IL-6, TNF-α, and IL-1β are pro-inflammatory cytokines that become elevated in both preeclampsia and preterm birth, reflecting the systemic inflammatory response. IL-8 is important for neutrophil recruitment and activation, while IL-10 and IL-4 are anti-inflammatory cytokines that may be dysregulated in these conditions. IFN-γ and IL-17 provide insights into T-cell responses that may contribute to placental dysfunction. The angiogenic factors VEGF, PlGF, and their antagonist sFlt-1 are particularly relevant for preeclampsia, as an imbalance favoring anti-angiogenic factors is a hallmark of the disease, as discussed in the executive summary of the workshop on preeclampsia 1. MCP-1 is valuable for assessing monocyte recruitment and placental inflammation.
Some key points to consider when evaluating these cytokines include:
- The importance of standardizing collection timing, ideally in the first trimester, to ensure reliable results and meaningful clinical correlations.
- The need for processing protocols and storage conditions to be standardized to prevent degradation of the samples and ensure accurate measurements.
- The potential for these cytokines to provide insights into the underlying mechanisms of preeclampsia and spontaneous preterm birth, and to inform the development of novel therapeutic strategies, as highlighted in research recommendations 1.
- The value of considering the complex interplay between inflammatory, immune, and angiogenic factors in the pathophysiology of these conditions, and the potential for biomarkers such as these cytokines to improve our understanding of disease mechanisms and to guide clinical management.
Overall, evaluating these 12 cytokines in maternal plasma in early pregnancy has the potential to provide valuable insights into the pathophysiology of preeclampsia and spontaneous preterm birth, and to inform the development of novel therapeutic strategies to improve outcomes for women and their babies.
From the Research
Cytokines to Evaluate in Preeclampsia and Spontaneous Preterm Birth
To determine the best cytokines to evaluate when studying preeclampsia and spontaneous preterm birth, several studies have investigated the role of various cytokines in these conditions. The following cytokines have been identified as potential biomarkers:
- IL-6: This cytokine has been shown to play a key role in the establishment of inflammation leading to spontaneous preterm birth 2. It has also been associated with term preeclampsia 3.
- IL-1β: This cytokine has been found to be significantly associated with a decrease in the log odds of preeclampsia, term preeclampsia, and preterm preeclampsia 3.
- TNF-α: This cytokine has been shown to be increased in amniotic fluid samples from patients with spontaneous preterm birth 4.
- IL-4 and IL-4 receptor: These cytokines have been found to be associated with preeclampsia, although the results were not consistent across statistical models 3.
- TNF-β: This cytokine has been found to be significantly associated with preeclampsia and term preeclampsia 3.
- IL-8: This cytokine has been investigated as a potential biomarker for preeclampsia, although its role is not yet fully understood 3.
- IL-10: This cytokine has been found to be decreased in preeclamptic women, suggesting a potential role in the pathogenesis of the disease 3.
- IFN-γ: This cytokine has been investigated as a potential biomarker for preeclampsia, although its role is not yet fully understood 3.
- IL-18: This cytokine has been found to be increased in preeclamptic women, suggesting a potential role in the pathogenesis of the disease 3.
- NAMPT: This cytokine has been found to be differentially expressed in women with early-onset preeclampsia 5.
- APOA1: This cytokine has been found to be differentially expressed in women with early-onset preeclampsia 5.
Top 12 Cytokines to Evaluate
Based on the available evidence, the following 12 cytokines may be considered for evaluation in studies of preeclampsia and spontaneous preterm birth:
- IL-6
- IL-1β
- TNF-α
- IL-4
- IL-4 receptor
- TNF-β
- IL-8
- IL-10
- IFN-γ
- IL-18
- NAMPT
- APOA1
These cytokines have been identified as potential biomarkers for preeclampsia and spontaneous preterm birth, and further research is needed to fully understand their roles in these conditions 2, 3, 5, 4.