Exploring the causal relationship between inflammatory cytokines and immunoinflammatory dermatoses: a Mendelian randomization study.

ABSTRACT

Objectives: Previous studies have shown that the onset and progression of several immunoinflammatory dermatoses are closely related to specific immune-inflammatory responses. To further assess the causal relationship between 41 inflammatory cytokines and immunoinflammatory dermatoses, we used a Mendelian randomization method. Methods: Mendelian two-sample randomization utilized inflammatory cytokines from a GWAS abstract containing 8,293 healthy participants as well as psoriasis (4,510 cases and 212,242 controls), atopic dermatitis (7,024 cases and 198,740 controls), and vitiligo (131 cases and 207,482 controls). The causal relationship between exposure and outcome was explored primarily using inverse variance weighting. In addition, multiple sensitivity analyses, including MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were simultaneously applied to enhance the final results. Results: The results showed that in clinical practice, IL-4 and IL-1RA were suggestive indicators of atopic dermatitis risk (OR = 0.878, 95% CI = 0.78-0.99, p = 0.036; OR = 0.902, 95% CI = 0.82-1.00, p = 0.045). SCGF-b was a suggestive indicator of psoriasis risk (OR = 1.095, 95% CI = 1.01-1.18, p = 0.023). IL-4 is a suggestive indicator of vitiligo risk (OR = 2.948, 95% CI = 1.28-6.79, p = 0.011). Conclusion: Our findings suggest that circulating inflammatory cytokines may play a crucial role in the pathogenesis of chronic skin inflammation. IL-4 and IL-1RA may have inhibitory roles in the risk of developing atopic dermatitis, while SCGF-b may have a promoting role in the risk of developing psoriasis. Furthermore, IL-4 may contribute to the risk of developing vitiligo. These results provide insights into further understanding the mechanisms of chronic skin inflammation and offer new targets and strategies for the prevention and treatment of related diseases.