Serum levels of IL-4, IL-13 and IL-33 in patients with age-related macular degeneration and myeloproliferative neoplasms

Abstract

Immune responses play a key role in the pathogenesis and progression of myeloproliferative neoplasms (MPN) and age-related macular degeneration (AMD). Recent studies suggested using MPNs as a “Human Inflammation Model” of drusen development and previous results showed interleukin-4 (IL-4) dysregulation in MPN and AMD. IL-4, IL-13 and IL-33 are all cytokines involved in the type 2 inflammatory response. This study investigated the cytokine levels of IL-4, IL-13 and IL-33 in serum of MPN and AMD patients. This cross-sectional study included 35 patients with MPN with drusen (MPNd) and 27 with MPN and normal retinas (MPNn), 28 patients with intermediate AMD (iAMD) and 29 with neovascular AMD (nAMD). With immunoassays, we quantified and compared levels of IL-4, IL-13 and IL-33 in serum between the groups. The study was conducted at Zealand University Hospital, Roskilde, Denmark, between July 2018 and November 2020. The serum levels of IL-4 were significantly higher in the MPNd group than in the MPNn group (p = 0.003). In regard to IL-33, the difference between MPNd and MPNn was not significant (p = 0.069), however, when subdivided into subgroups, a significant difference was found between polycythemia vera patients with drusen and those without drusen (p = 0.005). We found no IL-13 difference between the MPNd and MPNn groups. Our data didn’t show any significant IL-4 or IL-13 serum level difference between the MPNd and iAMD groups but in regard to IL-33, data recorded a significant serum level difference between the two groups. There was no statistically significant difference between the MPNn, iAMD and nAMD groups in levels of IL-4, IL-13 and IL-33. These findings suggested that the serum levels of IL-4 and IL-33 might play a role in drusen development in MPN patients. The results might represent the type 2 inflammatory arm of the disease. The findings support the association between chronic inflammation and drusen.

Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy

“… 23 Systemic IL-4 is elevated in a number of non-ocular pathologies, including systemic lupus erythematosus (SLE), 39 , 40 active psoriasis vulgaris, 41 tropical endomyocardial fibrosis, 42 atopic dermatitis, and atopic rhinitis 43 with a positive association between levels of IL-4 and disease severity in multiple sclerosis 44 and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome. 45 In ocular pathologies, a recent study by Gotfredsen et al, 29 compared serum levels of IL-4 between patients with myeloproliferative disorders with and without drusen, iAMD, and nvAMD. These authors did not find any statistically significant differences in iAMD compared to the other groups.…”

“…IL-4 is a pleotropic immunomodulatory cytokine with an important role in regulating the pathogenic immune response in chronic inflammatory disease. 23 – 28 To our knowledge, systemic IL-4 characterization data in iAMD 29 and GA is still emerging. Thus, the purpose of the research described herein was to investigate the role of IL-4 specifically in iAMD and GA to further define inflammatory pathways and potential systemic biomarkers involved in disease pathophysiology.…”