Cytomegalovirus Infection Drives a Distinct Mucosal and Systemic Cytokine Signature in Ulcerative Colitis Publisher Pubmed



Izadi N ; Shirmohammadi M ; Daryani N E ; Behboudi E ; Baghi H B ; Oskouee M A ; Sadeghipoor S ; Yazdani S ; Azadi A ; Naghili B ; Aghazadeh M ; Poortahmasebi V
Source: Virology Journal Published:2026

Abstract

Purpose: Ulcerative colitis (UC) is a chronic inflammatory bowel disease in which cytomegalovirus (CMV) reactivation has been linked to severe and steroid-refractory cases. However, the effect of CMV on cytokine regulation in UC remains unclear. This study investigated colonic and systemic cytokine profiles in CMV-positive and CMV-negative UC patients. Methods: A total of 190 UC patients were enrolled, including 90 CMV-positive and 100 CMV-negative cases. CMV status was confirmed by molecular and histopathological tests. Colonic gene expression of cytokines (TNF-α, IL-1β, IL-6, IL-17 A, IFN-γ, TGF-β, IL-8, IL-12, and RANTES) was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and serum concentrations were assessed using enzyme-linked immunosorbent assay (ELISA). Results: Demographic and clinical features were comparable between groups. CMV-positive patients showed higher colonic mRNA expression and serum concentrations of TNF-α, IL-1β, IL-6, and IL-17 A compared to CMV-negative patients (all p < 0.05). In contrast, IFN-γ, TGF-β, IL-8, IL-12, and RANTES did not differ significantly. Notably, CMV tissue viral load was significantly higher in patients with moderate to severe disease (Mayo score ≥ 6) and showed a positive correlation with plasma viral load (r = 0.664, p < 0.01). Multivariable logistic regression analysis adjusted for Mayo score confirmed that elevated TNF-α, IL-1β, and IL-6 remained independently associated with CMV positivity. These findings indicate a selective pro-inflammatory cytokine pattern rather than generalized immune activation. Conclusion: CMV infection in UC is associated with selective upregulation of pro-inflammatory cytokines at both mucosal and systemic levels. These findings highlight CMV as a potential driver of immune amplification in UC and support cytokine profiling as a tool for risk stratification and management of affected patients. © The Author(s) 2026.