James Chung

Background: Chronic inflammation is a prolonged immune response that fails to resolve an initial injury or remove the inciting stimulus.¹ Inflammation is a complex biological process that involves multiple ranges of external and internal stimuli that functions as part of the immune system to promote repair and cellular adaptation at the site of tissue damage.¹ Once acute inflammation progresses chronic inflammation, the process is mediated by pro-inflammatory mediators such as interleukin-1 (IL-1) and interleukin-6 (IL-6), which are also present during the initial acute inflammatory response to drive tissue repair.² Depending on the location and duration of injury, chronic circulation of these inflammatory mediators may lead to tissue damage and remodeling, and the recruitment of other cellular mediators, which then promote the release of more inflammatory and destructive molecules, which can ultimately lead to chronic disease, such as breast cancer, heart failure, and alcohol liver disease.^1,2,3

Research Objectives: The purpose of this literature review was to evaluate the role of inflammatory biomarkers in chronic inflammatory diseases and to examine their potential use in a clinical setting to monitor disease progression and cancer risk.

Search Methods: An online search in the Texas A&M University library and the PubMed database was conducted from 2017 to 2026 using the following key terms: “TNF-α”, “IL-1”, “IL-6”, “chronic inflammation”, “cancer”, and “inflammatory response”.

Results: Together, TNF‑α, IL‑1, and IL‑6 activate overlapping signaling pathways in stromal and parenchymal cells, including p38 MAPK, PI3K/Akt, NF‑κB, and JAK/STAT3, which sustain cytokine production, leukocyte recruitment, and tissue remodeling in chronic inflammation.^2,3,4,5 Persistent activation of these pathways creates a  microenvironment characterized by oxidative stress, DNA damage, and fibro-inflammatory remodeling under compensatory hyperproliferation.^1,2,4 In the MHT-ALD model, Ki-67, PCNA, and GSTP1 provides a mechanistic link between sustained TNF-α, IL-1, and the IL-6 pathway and eventual progression to hepatocellular carcinoma.^1,4 Measuring circulating inflammatory markers (e.g., IL-6, fibrinogen, CRP) together with proliferation or cancer-associated biomarkers (e.g., Ki-67, GSTP1) may allow monitoring of both chronic inflammatory activity and the transition from benign injury to malignant transformation in high-risk patients. ^1,3

Conclusion: The literature supports the clinical relevance of the body’s inflammatory response and the detection of the biomarkers to aid in identifying specific diseases and to help monitor disease progression and transformation. Future studies should integrate and potentially be use these inflammatory pathways to therapeutically stunt progressive chronic inflammatory, or limit systemic inflammatory responses to tissue-specific systems for individualistic treatments.

Works Cited:

1. Tobias DK, Akinkuolie AO, Chandler PD, et al. Markers of Inflammation and Incident Breast Cancer Risk in the Women’s Health Study. Am J Epidemiol. 2018;187(4):705-716. doi:10.1093/aje/kwx250
2. Turner NA, Mughal RS, Warburton P, O’Regan DJ, Ball SG, Porter KE. Mechanism of TNFalpha-induced IL-1alpha, IL-1beta and IL-6 expression in human cardiac fibroblasts: effects of statins and thiazolidinediones. Cardiovasc Res. 2007;76(1):81-90. doi:10.1016/j.cardiores.2007.06.003
3. Alarcón-Sánchez BR, Idelfonso-García OG, Guerrero-Escalera D, et al. A model of alcoholic liver disease based on different hepatotoxics leading to liver cancer. Biochem Pharmacol. 2024;228:116209. doi:10.1016/j.bcp.2024.116209
4. Buha I, Škodrić-Trifunović V, Adžić-Vukičević T, et al. Relevance of TNF-α, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients. J Infect Dev Ctries. 2019;13(5):419-425. Published 2019 May 31. doi:10.3855/jidc.10949
5. Zegeye MM, Lindkvist M, Fälker K, et al. Activation of the JAK/STAT3 and PI3K/AKT pathways are crucial for IL-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells. Cell Commun Signal. 2018;16(1):55. Published 2018 Sep 5. doi:10.1186/s12964-018-0268-4