Modulation of Interleukin-35 In the Immune Response to H. Pylori Infection

Background: Infection with Helicobacter pylori is a common disease of the digestive system, normally associated with several degrees of gastritis as well as chronic inflammation. Interleukin-35 (IL-35) is an emerging anti-inflammatory cytokine that mediates regulatory immunity; however, little research has been directed toward its participation in the pathogenesis of H. pylori. Objectives: To assess serum IL-35 levels in patients infected with H. pylori and correlate them with the severity and duration of the disease. Methods: This cross-sectional study was done on 80 patients who were clinically suspected to be infected with H. pylori (44 males and 36 females; age range 15–63 years) attending Al-Najaf General Hospital, Iraq, from February 2024 to March 2025. Stool antigen tests confirmed the presence of H. pylori infection. Serum IL-35 concentrations were measured by a sandwich ELISA method. Classification of participants was done according to the status of infection (positive vs. negative), severity of gastritis (mild, moderate, severe), and chronicity of the infection (acute vs. chronic). Results: Out of 80 participants, 58 (72.5%) were positive for H. pylori. The levels of IL-35 were significantly decreased in H. pylori-positive individuals (48.37 ± 22.33 pg/ml) as compared to negatives (58.54 ± 11.45 pg/ml, p =0 .0456). Among the infected patients, the levels of IL-35 varied significantly with the severity of gastritis; mild (35.7 ± 8.09), moderate (51.3 ± 11.11), severe (60 .2 ±17 .22) (F=21 .5, p<0 .0001). The concentrations of IL-35 were also significantly higher in chronic cases (62 .54±12 .32 pg/ml) than acute cases (34 .22±8 .54 pg/ml, p=0.000). Conclusions: IL-35 is low in early H. pylori infection and seems to go up with more gastritis severity and duration, hinting a modulatory role in the host immune response. These findings support potential involvement of IL-35 in immunopathogenesis and progression of H. pylori related gastric inflammation.