The Impact of Growth Factors on Sjögren Syndrome Risk

Relationship Between Growth Factors and Sjögren Syndrome

Sjögren syndrome (SS) is a chronic autoimmune disorder characterized by dry mouth and dry eyes, resulting from the immune system’s attack on the exocrine glands. Recent studies have indicated a potential relationship between growth factors and the risk of developing Sjögren syndrome. Growth factors such as Interleukin-10 (IL-10) and Interleukin-18 (IL-18) are known to play crucial roles in regulating immune responses. IL-10 is primarily an anti-inflammatory cytokine, whereas IL-18 acts as a pro-inflammatory cytokine, suggesting a delicate balance between these factors might influence the susceptibility to autoimmune diseases, including SS.

Investigations have highlighted the dual role of these cytokines in the pathogenesis of autoimmune diseases, where they can either exacerbate or mitigate inflammation based on their expression levels and the context in which they operate. For instance, lower levels of IL-10 may correlate with increased disease activity and severity in autoimmune conditions, while elevated IL-18 levels have been associated with enhanced inflammatory responses that can lead to tissue damage.

Analysis of IL-10 and IL-18 in Inflammatory Diseases

The intricate relationship between IL-10 and IL-18 has been studied across various inflammatory diseases. A study by Zheng (2025) found that both IL-10 and IL-18 are significantly downregulated in patients with pneumonia and sepsis, correlating with poorer prognoses. These findings suggest that dysregulation of these cytokines may contribute to the severity of inflammatory responses in various diseases.

In the context of Sjögren syndrome, it has been observed that patients often exhibit altered levels of these growth factors. For example, research indicates that patients with SS have significantly lower salivary EGF levels compared to healthy controls, which may link to the severity of intraoral manifestations (Zheng, 2025). Furthermore, another study found that salivary transforming growth factor alpha levels were elevated in SS patients, potentially indicating a compensatory mechanism in response to inflammation.

The Role of Cytokines in Autoimmune Pathogenesis

Cytokines such as IL-10 and IL-18 are pivotal in the regulation of immune responses, and their dysregulation can lead to autoimmune pathogenesis. In Sjögren syndrome, the balance between these cytokines may be disrupted, promoting an environment conducive to autoimmunity. The interaction between IL-10 and IL-18 is central to understanding the immune dysregulation observed in SS.

IL-10 functions to limit excessive inflammation by inhibiting the production of pro-inflammatory cytokines and promoting regulatory T cell responses. Conversely, IL-18 enhances T cell activation and promotes the production of interferon-gamma, contributing to a pro-inflammatory state. This duality suggests that the therapeutic modulation of these cytokines could play a role in managing autoimmune diseases, including Sjögren syndrome.

Methodological Insights from Mendelian Randomization Studies

Mendelian randomization (MR) offers a robust framework for understanding causal relationships by using genetic variants as instrumental variables. In the context of Sjögren syndrome and growth factors, MR can help elucidate whether genetic predispositions to altered growth factor levels causally influence the risk of developing SS.

A recent study employing MR techniques found no significant causal relationship between genetic variants associated with growth factor levels and the risk of Sjögren syndrome. This suggests that while growth factors may play a role in the pathogenesis of SS, they might not act as direct risk factors for the disease onset. These findings emphasize the importance of considering broader biological pathways and environmental interactions when investigating complex autoimmune diseases.

Implications for Future Research and Clinical Practice

The findings regarding the relationship between growth factors and Sjögren syndrome underscore the need for further research to unravel the complexities of autoimmune pathogenesis. Future studies should focus on:

1. Longitudinal Studies: To assess changes in growth factor levels over time and their correlation with disease progression.
2. Genetic Studies: To explore additional genetic variants associated with growth factor signaling pathways that may impact the risk of developing SS.
3. Targeted Therapies: Investigating the potential of modulating IL-10 and IL-18 levels as therapeutic strategies in managing Sjögren syndrome.
4. Multi-Omics Approaches: Integrating genomic, transcriptomic, and proteomic data to understand the multifaceted nature of SS and identify new biomarkers for diagnosis and treatment.

Table 1: Summary of Findings on IL-10 and IL-18 in Sjögren Syndrome

Frequently Asked Questions (FAQ)

What is Sjögren syndrome?
Sjögren syndrome is an autoimmune disorder characterized by dry mouth and dry eyes due to the immune system attacking the body’s moisture-producing glands.

How do IL-10 and IL-18 influence autoimmune diseases?
IL-10 is an anti-inflammatory cytokine that helps to limit excessive inflammation, while IL-18 is a pro-inflammatory cytokine that promotes immune responses. The balance between these cytokines is crucial in the context of autoimmune diseases.

What is Mendelian randomization?
Mendelian randomization is a method that uses genetic variants as instrumental variables to determine causal relationships between modifiable risk factors and health outcomes, minimizing bias from confounding factors.

What are the implications of the findings for clinical practice?
The findings suggest that modulating growth factors like IL-10 and IL-18 might be a potential therapeutic strategy for managing Sjögren syndrome and other autoimmune diseases.

Why is further research necessary?
Further research is essential to clarify the complex relationships between growth factors and Sjögren syndrome, identify new therapeutic targets, and improve patient outcomes.

References

1. Zheng, H. (2025). The critical immunoregulatory roles and molecular mechanisms of IL-10 and IL-18 genes in pneumonia and sepsis. Medicine. Retrieved from https://pubmed.ncbi.nlm.nih.gov/12014067/

2. Kurek, J., Fraser, M. P., Nakamoto, B. J., Kidd, K. A., & Edge, C. B. (2025). Legacy DDT and its metabolites in Brook Trout from lakes within forested watersheds treated with aerial applications of insecticides. PLoS One. Retrieved from https://doi.org/10.1371/journal.pone.0320665

3. Yin, Y., Liao, M., Yu, Y., Hu, G., Yang, X., Guo, C., & Yu, R. (2025). Interference between rheumatoid arthritis and autoimmune thyroid diseases: A bidirectional Mendelian randomization. Medicine. Retrieved from https://pubmed.ncbi.nlm.nih.gov/12014076/

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