IL-4 and IL-13 induce equivalent expression of traditional M2 markers and modulation of reactive oxygen species in human macrophages

• Published in: Scientific reports Vol. 13; no. 1; p. 19589
• Main Authors: Scott, Tara E., Lewis, Caitlin V., Zhu, Mingyu, Wang, Chao, Samuel, Chrishan S., Drummond, Grant R., Kemp-Harper, Barbara K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.11.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/127; 631/250/2504/342; 631/80/86; 692/699; Cardiovascular disease; Cardiovascular diseases; Cytokines; Humanities and Social Sciences; Interleukin 13; Interleukin 2 receptors; Interleukin 4; Lymphocytes T; Macrophages; multidisciplinary; Reactive oxygen species; Science; Science (multidisciplinary); Stat1 protein; Stat3 protein; Stat6 protein; Superoxide
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-46237-2

In cardiovascular disease, pathological and protective roles are reported for the Th2 cytokines IL-4 and IL-13, respectively. We hypothesised that differential effects on macrophage function are responsible. Type I and II receptor subunit (IL-2Rγ, IL-4Rα and IL-13Rα1) and M2 marker (MRC-1, CCL18, CCL22) expression was assessed via RT-qPCR in IL-4- and IL-13-treated human primary macrophages. Downstream signalling was evaluated via STAT1, STAT3 and STAT6 inhibitors, and IL-4- and IL-13-induced reactive oxygen species (ROS) generation assessed. IL-4 and IL-13 exhibited equivalent potency and efficacy for M2 marker induction, which was attenuated by STAT3 inhibition. Both cytokines enhanced PDBu-stimulated superoxide generation however this effect was 17% greater with IL-4 treatment. Type I IL-4 receptor expression was increased on M1-like macrophages but did not lead to a differing ability of these cytokines to modulate M1-like macrophage superoxide production. Overall, this study did not identify major differences in the ability of IL-4 and IL-13 to modulate macrophage function, suggesting that the opposing roles of these cytokines in cardiovascular disease are likely to be via actions on other cell types. Future studies should directly compare IL-4 and IL-13 in vivo to more thoroughly investigate the therapeutic validity of selective targeting of these cytokines.