Association of interleukin-6 and TNF-α genetic variants with pneumonia- induced sepsis in ICU adult patients

Khanany, Farida Mohamed; Kamal, Hany; El maghraby, Ahmed Mohamed ali; Abbas, Rania Mohamed; Shata, Aalaa K.; Madbouly, Medhat; Mahmoud, Mahmoud Mohsen; Mabrouk, Khaled; Osman, Enas Ahmed

doi:10.21608/mid.2025.383648.2779

	Association of interleukin-6 and TNF-α genetic variants with pneumonia- induced sepsis in ICU adult patients
Microbes and Infectious Diseases
Articles in Press, Accepted Manuscript, Available Online from 29 July 2025
Document Type: Original Article
DOI: 10.21608/mid.2025.383648.2779
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Authors
Farida Mohamed Khanany ¹; Hany Kamal¹; Ahmed Mohamed ali El maghraby²; Rania Mohamed Abbas³; Aalaa K. Shata⁴; Medhat Madbouly⁵; Mahmoud Mohsen Mahmoud⁴; Khaled Mabrouk¹; Enas Ahmed Osman¹
¹Clinical Chemistry Department, Theodor Bilharz Research Institute, Giza, Egypt
²Intensive Care Department, Theodor Bilharz Research Institute
³Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
⁴Chest Department Faculty of Medicine, Ain Shams University, Cairo, Egypt
⁵Radiology Department, Theodor Bilharz Research Institute, Giza, Egypt
Abstract
Background: Pneumonia-induced sepsis and septic shock are major global reasons for mortality. A cytokine storm, characterized by enormously elevated circulating cytokines in response to infection, involves various cytokines, such as interleukin-6 (IL-6) along with tumor necrosis factor-alpha (TNF-α), which are essential in the pathogenesis of this condition. Genetic polymorphisms have been linked to variations in producing these cytokines. Aim: We evaluated the influence of genetic variations TNF-α rs361525 and TNF-α rs1800750, together with IL-6 rs1800795 and IL-6 rs1800796, on pneumonia-induced sepsis and septic shock. Methods: This case-control research assessed genetic variation in TNF-α and IL-6 by the TaqMan real-time polymerase chain reaction in a cohort of 316 cases. 90 patients (28.5%) were diagnosed with pneumonia-induced sepsis, 60 patients (18.9%) with pneumonia-induced septic shock, and 166 healthy individuals (52.5%) served as controls. Results: In the TNF-α rs1800750, the GA genotype was significantly more common in cases with pneumonia-induced sepsis and septic shock when compared to the control group. The AA genotype was significantly more common in pneumonia-induced septic shock cases than in controls. TNF-α rs361525 demonstrated no significant changes across the groups. The CG and GG genotypes in the IL-6 rs1800795 were significantly higher in pneumonia-induced sepsis and septic shock cases compared to controls. The CG genotype of the IL-6 rs1800796 revealed a significantly lower proportion in the pneumonia-induced septic shock group as compared to controls. Conclusion: We found that TNF-α rs1800750, IL-6 rs1800795, and rs1800796 have a potential impact on pneumonia-induced sepsis and septic shock.
Keywords
Cytokines; infections; septic shock; polymorphism


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