Expression of Ifng and IL4 Genes in Protecting Against UVB-Induced Photoaging and Inflammation: A Comprehensive Review

Abstract

To review the role of IFNG and IL4 gene expression in UVB-induced photoaging and inflammation, and to highlight the therapeutic potential of pineapple (Ananas comosus) peel extract, particularly in advanced topical formulations, in modulating these cytokines to protect and repair the skin. UVB radiation is a major extrinsic factor in skin aging, promoting excessive reactive oxygen species (ROS) generation, oxidative damage, and activation of redox-sensitive pathways such as NF-kB and AP-1. This process leads to chronic low-grade inflammation (inflammaging), extracellular matrix degradation, wrinkle formation, and pigmentary disorders, including post-inflammatory hyperpigmentation. IFNG is a key pro-inflammatory cytokine that, when overexpressed, sustains tissue-damaging inflammation and contributes to melanogenesis through post-translational regulation of tyrosinase. In contrast, IL4 is an immunoregulatory cytokine that suppresses pro-inflammatory mediators, promotes Th2 skewing, supports M2 macrophage polarization, and facilitates wound healing and extracellular matrix remodeling. An imbalance characterized by elevated IFNG and insufficient IL4 is a critical feature of UVB-induced photoaging. Pineapple peel, rich in bromelain, phenolic compounds, and other antioxidants, has demonstrated significant antioxidant and immunomodulatory activities, including reduction of pro-inflammatory cytokines and enhancement of anti-inflammatory responses. Formulating pineapple peel extract into topical delivery systems may improve skin penetration, stability, and local bioavailability, thereby enhancing its ability to downregulate IFNG, upregulate IL4, and mitigate UVB-induced structural and functional skin damage.