Exploring the innate immune response in polycystic liver disease

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2024-12, Vol.184, p.156800, Article 156800
• Main Authors: Duijzer, Renée, Dalloyaux, Daisy, Boerrigter, Melissa M., Lemmers, Heidi, Dijkstra, Helga, van Emst, Liesbeth, te Morsche, René H.M., Jaeger, Martin, Joosten, Leo A.B., Drenth, Joost P.H.
• Format: Article
• Language: English
• Subjects: ADPKD; ADPLD; Autosomal dominant polycystic kidney disease; Autosomal dominant polycystic liver disease; IFNγ; IL-17; IL-1Ra; IL-1β; IL-22; IL-6; IL-8; Peripheral blood mononuclear cells; PLD; PMBC; Polycystic liver disease; TNF
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2024.156800

[Display omitted] •PLD patients consistently showed higher IL-6 concentrations than controls.•PLD patients had higher IL-1β and IL-1Ra concentrations in response to S. aureus and C. albicans.•Controls had higher IL-8 and TNF concentrations in response to Gram-negative bacteria,•No differences were found in IL-17, IL-22, and IFN-γ concentrations after 7 days.•Differences were independent of demographic and clinical factors. The role of the innate immune system in polycystic liver disease (PLD) has been underexplored despite its potential importance in disease progression. This study explores the innate immune response in PLD patients by analyzing cytokine production of peripheral blood mononuclear cells (PBMCs) in response to various pathogens compared to healthy controls. Samples were collected from patients with ADPLD or ADPKD and PLD. PBMCs were isolated and stimulated with LPS (1 ng), LPS (10 ng), E. coli, K. pneumoniae, S. aureus, and C. albicans. ELISA was used to measure TNF, IL-1β, IL-1Ra, IL-6, and IL-8 concentrations after 24 hours, and IL-17, IL-22, and IFNγ concentrations after 7 days. Control samples were matched for age and gender. 104 patients and 12 controls were included. PLD patients showed consistent increased IL-6 concentrations compared to controls. Other cytokine levels varied per stimulus. Controls showed higher IL-8 and TNF concentrations in response to Gram-negative bacteria, while PLD patients showed higher IL-1β and IL-1Ra levels in response to S. aureus and C. albicans. No clear differences were found in IL-17, IL-22, and IFN-γ concentrations after 7 days. These observed differences were independent of demographic and clinical parameters. Compared to healthy controls, the PLD patients innate immune system shows an altered response when stimulated by various pathogens. These findings underscore the importance of further investigation into the underlying mechanisms as this might help our understanding disease progression and be a potential target for new therapies.