interleukin (IL)-6

Overview

interleukin-6 (IL-6) is a pleiotropic proinflammatory cytokine with broad roles in innate and adaptive immunity, acute-phase responses, hematopoiesis, and tissue injury signaling. It is produced by multiple cell types, including macrophages, monocytes, fibroblasts, endothelial cells, and other stromal or immune cells, and acts through the IL-6 receptor complex to activate downstream pathways such as JAK/STAT, with additional crosstalk to NF-κB, MAPK, and related inflammatory signaling networks. Because of this central position in inflammatory biology, IL-6 is widely used as a biomarker of immune activation and as a mechanistic readout in studies of infection, autoimmune disease, metabolic injury, neuroinflammation, and tissue repair.

In biomedical research, IL-6 is often interpreted alongside other inflammatory mediators such as TNF-α, IL-1β, IL-8, IL-10, and IL-17A, as well as pathway-associated entities including nuclear factor kappa B, MAPK/ERK/JNK signaling pathways, NLRP3 inflammasome, AMPK/mTOR, and cGAS-STING/NF-κB signaling pathway. Its circulating or tissue levels are frequently measured to assess disease severity, treatment response, or the anti-inflammatory effects of candidate compounds, biologics, or procedures.

Focus of Latest Publications

Recent publications in which IL-6 was investigated as a target consistently frame it as a key inflammatory readout across diverse disease models and intervention studies.

Several studies examined natural products, food-derived compounds, or formulation strategies for their ability to suppress IL-6 as part of an anti-inflammatory effect. In wine-processed Radix Paeoniae Rubra, multi-platform mass spectrometry and molecular docking suggested strong binding affinities to IL-1β, IL-6, and TNF-α, supporting a mechanistic basis for enhanced anti-inflammatory functionality. Similarly, spirulina immunoactive peptide-based nanoemulsions carrying astaxanthin were reported to reduce LPS-induced NO production and lower TNF-α, IL-6, and IL-1β in RAW264.7 macrophages, with the effect attributed to inhibition of NF-κB pathway activation. Soybean hull hemicellulose-derived oligosaccharides also downregulated IL-6 secretion in LPS-induced RAW264.7 cells, and biogenic selenium extract-mediated and total Convolvulus oxyphyllus extracts were evaluated for their ability to suppress IL6 and COX2 expression. Additional anti-inflammatory candidates, including taurine, cafestol, betulinic acid, methylated tirilazad, indole-3-propionic acid, and myrtucommulone B analogs, were each associated with reduced IL-6 levels in models of diabetic nephropathy, osteoporosis, spinal cord injury, colitis, neuroinflammation, or inflammatory bowel disease. These studies collectively place IL-6 at the center of compound screening and mechanistic validation in inflammatory pharmacology.

IL-6 was also used as a biomarker in clinical and translational studies of inflammatory disease. In severe traumatic brain injury, IL-6 was among the key mediators consistently elevated in both blood and cerebrospinal fluid, indicating a robust early inflammatory response across compartments. In atopic dermatitis patients treated with dupilumab, IL-6 was measured alongside IL-17A, TSLP, IFNγ, TNFα, IL-2, IL-12p70, IL-23, and IL-31 to assess seasonal variation in cytokine profiles. In periodontitis among patients with severe obesity, higher salivary IL-6 levels were associated with worsened periodontal parameters and oral microbiota dysbiosis. In monozygotic twins discordant for pain-related temporomandibular disorder, within-pair differences in IL-6 and the IL-6/IL-10 ratio were identified, supporting a role for inflammatory balance in symptom discordance. In coronary artery disease, plasma IL-6 was measured together with TNF-α, IL-1β, IL-10, and coagulation factor V-related variables to explore crosstalk between monocytes and coagulation factor VIIa in inflammatory amplification. In dogs with thoracolumbar intervertebral disc disease receiving acupuncture, IL-6 was included among plasma inflammatory biomarkers assessed in relation to treatment. A pilot study of electroacupuncture in chronic nonspecific low back pain also reported a significant decrease in IL-6, accompanied by increased IL-10, suggesting a shift toward a less inflammatory cytokine profile.

IL-6 has further been used in mechanistic studies of immune signaling and disease pathogenesis. In rheumatoid arthritis, imaging-guided macrophage-targeted nanotheranostics were developed in the context of synovial M1 macrophages that secrete TNF-α, IL-1, and IL-6 and activate JAK-STAT/NF-κB pathways. In acute gouty arthritis, RGFP966 reduced serum IL-6 together with IL-1β, IL-18, and TNF-α while suppressing AIM2 inflammasome-related proteins. In diabetic nephropathy, taurine and cafestol both reduced IL-6 in serum or renal tissue, alongside changes in HMGB1/TLR4/MyD88/NF-κB or Keap1-Nrf2 axis signaling. In acute liver injury, a selective CSF1R inhibitor lowered circulating TNF-α and IL-6, consistent with attenuation of inflammatory signaling. In spinal cord injury and astrocyte inflammation, indole-3-propionic acid reduced IL-6 expression in astrocytes in vitro and in vivo through the AHR/NF-κB/MAPK axis. In atopic dermatitis, Chlorophytum borivilianum and related interventions were associated with downregulation of IL-6 gene expression together with IL-4, IL-13, and TNF-α. In DSS-induced colitis, methylated tirilazad reduced IL-6 and TNF-α while increasing IL-10 and restoring barrier markers such as Occludin and ZO-1.

IL-6 also appears in diagnostic and immunological technology development. A DNA-engineered immunosensing platform was used to detect IL-6 with very high sensitivity, alongside NGAL and cTnI, illustrating its value as a clinical protein biomarker. In a study of humoral contributions to checkpoint blockade therapy, autoantibodies against proteins in the IL-6 pathway were associated with better therapeutic responses, especially when neutralizing, suggesting that endogenous modulation of IL-6 signaling may influence immunotherapy outcomes. Across these studies, IL-6 functions both as a mechanistic target and as a measurable indicator of inflammatory state, treatment response, and pathway modulation.

Key Publications

• NEWApr Chemical transformations and polyphenol enrichment in wine-processed Radix Paeoniae Rubra: A multi-platform mass spectrometry approach to enhanced anti-inflammatory functionality. (Food chemistry, 2026, PMID 42000152): "Molecular docking showed strong binding affinities (ΔG ≤ -5.0 kcal/mol) to IL-1β, IL-6, and TNF-α."
• NEWApr Utilizing spirulina immunoactive peptide-based nanoemulsions to enhance the stability, bioaccessibility and synergistic immune activity of astaxanthin. (Food chemistry, 2026, PMID 41980364): "IAP and AST exhibited synergistic immunomodulatory activity by effectively suppressing LPS-induced NO production and reducing the levels of inflammatory cytokines (TNF-α, IL-6, IL-1β) in RAW264.7 cells, which was attributed to the inhibition of NF-κB pathway activation."
• Jun 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 A Dynamic and Complex Early Inflammatory Response in Blood and Cerebrospinal Fluid of Severe Traumatic Brain Injury Patients: A Dual Platform Analysis. (Inflammation, 2026, PMID 42360398): "Key mediators (IL-6, IL-8, IL-10) were consistently elevated in both compartments."
• Jun Seasonal variation in cytokine profiles in atopic dermatitis patients treated with dupilumab. (Journal of immunotoxicology, 2026, PMID 42360862): "Cytokines (interleukin [IL]-17A, thymic stromal lymphopoietin (TSLP), interferon (IFN)γ, tumor necrosis factor (TNFα), IL-2, IL-6, IL-12p70, IL-23, and IL-31) were measured during summer and winter under unstimulated and phorbol 12-myristate 13-acetate (PMA)/ionomycin-stimulated conditions."
• Jun Neuroprotective mechanisms of Thai traditional brain tonic Phy-Blica-O against LPS-induced neuroinflammation: Inhibition of NF-κB in microglia and mice. (PloS one, 2026, PMID 42361074): "PBO pretreatment significantly reduced LPS-induced overproduction of nitric oxide (NO) (from 15.69 ± 1.63 to 8.74 ± 0.25 μM at 250 μg/mL, p<0.001), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6 mRNA expression reduced by 25%, 31%, and 19%, respectively, p<0.05), and inflammatory mediators (iNOS and COX-2 protein expression decreased by 41% and 29%, respectively, p<0.05)."
• May Evaluating Dermal Bioactivity of Metal Additive Manufacturing Powders Using Human In Vitro and Ex Vivo Skin Models. (Chemical research in toxicology, 2026, PMID 42070096): "In HaCaT cells, MCP-1/CCL2, IL-6, and IL-8/CXCL8 were quantifiable but showed no significant changes following powder exposure."
• May Betulinic acid alleviates the inflammatory injury of osteoblasts in osteoporosis by augmenting autophagy via the AMPK-mTOR signaling pathway. (International journal of molecular medicine, 2026, PMID 42138188): "BA was revealed to alleviate bone loss in OVX rats and inhibit the expression of NOD-like receptor pyrin domain-containing 3 (NLRP3), Asc and caspase-1 in the femur of OVX rats, as well as suppress the release of inflammatory factors such as interleukin-1 β, interleukin-6, and tumor necrosis factor-α in the serum of rats."
• May Periodontitis in Patients With Severe Obesity: From the Oral and Gut Microbiota Dysregulation to the Visceral Adipose Tissue Inflammatory and Metabolic Disorders. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026, PMID 42037322): "Results show that patients with periodontitis exhibited an oral microbiota dysbiosis characterized by an increased abundance of bacteria from the red and orange complexes, worsened periodontal parameters (plaque index, bleeding index, gingival recession, probing depth and clinical attachment level), and higher IL-6 salivary levels."
• May DNA-engineered immunosensing platform for ultrasensitive detection of clinical protein biomarkers. (Biosensors & bioelectronics, 2026, PMID 41655520): "As proof of concept, DEISP was employed to detect the kidney injury biomarker neutrophil gelatinase-associated lipocalin (NGAL), the pro-inflammatory cytokine interleukin-6 (IL-6), and the cardiac troponin I (cTnI) associated with myocardial infarction, demonstrating remarkable sensitivity with limits of detection (LODs) of 0.025 pg mL-1 for NGAL, 0.026 pg mL-1 for IL-6, and 2.35 pg mL-1 for cTnI."