TNF

Overview

Tumor necrosis factor, commonly abbreviated TNF and often referred to as TNF-α in its soluble cytokine form, is a central pro-inflammatory signaling protein in the immune system. It is produced by multiple cell types, especially activated macrophages and T cells, and acts through TNF receptors to regulate inflammation, immune-cell activation, apoptosis, tissue remodeling, and host defense. Because of these broad effects, TNF is a major mediator in acute and chronic inflammatory disease and a frequent biomarker of inflammatory burden.

Biomedically, TNF is also a major therapeutic target. Excess TNF signaling is implicated in disorders such as rheumatoid arthritis, Crohn’s disease, diabetic complications, atherosclerosis, neuroinflammation, and tissue injury after ischemia or infection. Conversely, controlled TNF signaling can participate in regenerative or immune-reprogramming processes, as seen in recent studies of endometrial regeneration and immune microenvironment remodeling. This dual role makes TNF both a disease driver and a biologically important signaling node in tissue repair and immune regulation.

Focus of Latest Publications

Recent publications have examined TNF in a range of inflammatory and disease models, most often as a readout of immune activation or as a therapeutic target. In dogs with thoracolumbar intervertebral disc disease receiving acupuncture, plasma TNF-α was measured alongside neurological grading, HIF-1α, IL-6, and total plasma NAD(H). Neurological scores improved after treatment, and TNF-α showed significant treatment period-, disease phase-, and treatment method-dependent changes, with significant pre-post differences in the electroacupuncture group during both acute and preventive phases. These findings suggested that TNF-α may reflect phase- and method-dependent inflammatory responses after acupuncture, particularly with electroacupuncture.

TNF-α was also implicated in tissue regeneration and repair. In a mouse endometrial injury model integrated with human endometrial datasets, time-series single-cell and spatial omics showed that macrophages infiltrated early after injury and promoted the expansion and developmental reprogramming of SFRP4+ stromal cells during the regenerative phase. The study reported that macrophages promoted this reprogramming via TNF-α, and that TNF-α-induced SFRP4+ stromal cells enhanced regeneration after transplantation. In infected wound healing research, a biomineralized hydrogel incorporated TNF-α siRNA to silence TNF-α expression in macrophages, which reduced IL-6 and IL-1β, while also supporting antibacterial activity, angiogenesis, collagen deposition, and accelerated wound closure in mice.

Other studies evaluated TNF-α in neuroinflammation and drug discovery contexts. In a mouse model of polystyrene nanoplastic exposure, hippocampal damage and cognitive deficits were associated with oxidative stress, microglial activation, microglial extracellular trap formation, increased TNF-α and IL-1β, and neuronal ferroptosis; antioxidant treatment with N-acetylcysteine reduced these changes. In an Alzheimer's disease study, lawsone was assessed as a multitarget compound, and computational analyses showed binding affinity to TNF-α, while experimental work reported reduced proinflammatory markers including TNF-α together with improved cognitive and pathological outcomes. A separate in silico and in vitro study of a thiadiazole derivative identified notable affinity for the TNF binding site, with docking and molecular dynamics supporting a stable TNF-compound interaction, suggesting potential anticancer relevance.

Key Publications

• NEWJun Clinical investigation of plasma HIF-1α and inflammatory biomarkers in dogs with thoracolumbar intervertebral disc disease receiving acupuncture treatment. (Veterinary research communications, 2026, PMID 42371222): "...including hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and total plasma NAD(H) levels, in dogs with thoracolumbar intervertebral disc disease (TL-IVDD) undergoing acupuncture treatment."
• Jun Spatial and temporal single cell multi-omics in mice reveals macrophage-SFRP4+ stroma interactions promoting endometrial regeneration via TNF-α. (Cell reports, 2026, PMID 42234562): "Macrophages promote this reprogramming via tumor necrosis factor-alpha (TNF-α), and TNF-α-induced SFRP4+ stromal cells effectively enhance regeneration after transplantation."
• May Multitarget pharmacological effects of Lawsone in mitigating Alzheimer's disease. (European journal of pharmacology, 2026, PMID 42105996): "Expression of the proinflamatory markers, nuclear factor kappa B (NF-κB), c-Jun N terminal kinase (c-JNK), Tumor necrosis factor-α (TNF-α) and Alzheimer's associated proteins APP, Aβ1-42, and p-Tau were assessed through real time polymerase chain reaction (qPCR), enzyme linked immunosorbent assay (ELISA)."
• May Polystyrene nanoplastics induce hippocampal damage and cognitive deficits through oxidative stress-triggered microglial extracellular traps and neuronal ferroptosis. (Chemico-biological interactions, 2026, PMID 42070744): "This sustained neuroinflammatory response, characterized by the release of MiETs and increased levels of proinflammatory cytokines (Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β)), was closely associated with neuronal ferroptosis."
• May Lipid emulsion modulates myogenic and collagen-related gene expression in skeletal muscle of preterm fetal sheep. (Experimental physiology, 2026, PMID 41955312): "Similarly, genes related to inflammation, such as Tnfa (tumour necrosis factor α), Il-6 (interleukin 6), Tlr4 (Toll-like receptor 4) and Tlr2 (Toll-like receptor 2), were unaffected."
• May Programmable metal-nucleic acid biomineralized hydrogel for infected wound healing via mitochondrial regulation. (Acta biomaterialia, 2026, PMID 41941975): "Concurrently, siTNF-α silences TNF-α expression in macrophages, thereby reducing pro-inflammatory cytokines including interleukin-6 (IL-6) and IL-1β."
• Apr Exploration of a Novel Thiadiazole Derivative: Design, Synthesis, Biological Evaluation (In Vitro and in Silico), and DFT Studies. (Journal of fluorescence, 2026, PMID 41673348): "Molecular docking analyses revealed that thiadiazole 5 displayed a notable affinity toward the Tumor Necrosis Factor (TNF) binding site, reflected by a binding energy of -8.69 kcal/mol."