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Updated: Jun 10, 2025
A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.
Published on: February 14, 2021
Assessing the causal relationship between CRP, IL-1α, IL-1β, and IL-6 levels and intervertebral disc degeneration: a
Xin-An Yan1, Erdong Shen1, Aiyong Cui1
1Department of Pelvic and Acetabular Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, China.
Abstract:
Growing research has suggested an association between chronic inflammation and Intervertebral disc degeneration (IVDD), but whether there is a causal effect remains unknown. This study adopted two-sample Mendelian randomization (MR) approach to explore the etiological role of chronic inflammation in IVDD risk. Here, summary statistics for C-reactive protein (CRP), interleukin (IL)-1 , IL-1 , IL-6 expression and IVDD were obtained from genome-wide association studies (GWAS) of European ancestry. MR analyses were conducted by using inverse variance weighted (IVW), Wald Ratio, weighted median, and MR-Egger method. Sensitivity analyses were conducted to assess the robustness of the results. The MR analyses suggested a lack of causal association of CRP, IL-6 , and IL-1 levels on IVDD (CRP-IVDD: odds ratio [OR] = 0.97, 95% confidence interval [CI] 0.86-1.09, P = 0.583; IL-6-IVDD: OR = 1.04, 95% CI 0.86-1.27, P = 0.679; IL-1 -IVDD: OR = 1.09, 95%CI 1.00-1.18, P = 0.058). However, there was a sign of a connection between genetically elevated IL-1 levels and a decreased IVDD incidence (OR = 0.87, 95%CI 0.77-0.99, P = 0.03). Our findings suggest a connection between IL-1 levels and the risk of IVDD. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, the specific underlying mechanisms warrant further investigation.
Insights
This study investigated the causal link between chronic inflammation and Intervertebral Disc Degeneration (IVDD). While most inflammatory markers showed no effect, elevated Interleukin-1 (IL-1) levels were associated with reduced IVDD risk.
Area of Science:
- Genetics and Molecular Biology
- Inflammation Research
- Orthopedics and Spine Surgery
Background:
- Chronic inflammation is increasingly linked to Intervertebral Disc Degeneration (IVDD).
- The causal relationship between inflammatory markers and IVDD risk remains unclear.
- Understanding this link is crucial for developing targeted IVDD prevention and treatment strategies.
Purpose of the Study:
- To investigate the etiological role of chronic inflammation in Intervertebral Disc Degeneration (IVDD) using a Mendelian randomization approach.
- To assess the causal effect of specific inflammatory markers, including C-reactive protein (CRP), Interleukin-6 (IL-6), and Interleukin-1 (IL-1), on IVDD risk.
- To explore potential genetic predispositions influencing the association between inflammation and IVDD.
Main Methods:
- Employed a two-sample Mendelian randomization (MR) approach utilizing summary statistics from large-scale genome-wide association studies (GWAS) of European ancestry.
- Analyzed genetic variants associated with C-reactive protein (CRP), Interleukin-6 (IL-6), and Interleukin-1 (IL-1) levels.
- Applied multiple MR methods including Inverse Variance Weighted (IVW), Wald Ratio, Weighted Median, and MR-Egger, alongside sensitivity analyses to ensure result robustness.
Main Results:
- Mendelian randomization analyses indicated no significant causal association between genetically predicted levels of CRP, IL-6, and IL-1 and the risk of IVDD.
- A suggestive inverse association was observed between genetically elevated Interleukin-1 levels and a decreased incidence of IVDD (OR = 0.87, 95% CI 0.77-0.99, P = 0.03).
- The association for IL-1 was based on a single nucleotide polymorphism (SNP), precluding detailed heterogeneity and pleiotropy testing.
Conclusions:
- The study suggests a potential inverse relationship between Interleukin-1 levels and Intervertebral Disc Degeneration (IVDD) risk.
- No causal link was found between CRP, IL-6, or IL-1 and increased IVDD risk.
- Further research with more robust genetic evidence is warranted to elucidate the specific mechanisms underlying the observed association between IL-1 and IVDD.
