clodronate disodium / Generic mfg. - LARVOL DELTA

Bidirectional Crosstalk Between Sleep and Pulmonary Arterial Hypertension (ERS 2026) - "Lastly, concurrent improvement of sleep with melatonin and reduction of inflammation with clodronate inhibited pulmonary vascular remodeling and mitigated PAH. PAH causes sleep disruption, which in turn promotes lung inflammation, increases PASMC proliferation, and further exacerbates PAH. The relationship between PAH and sleep disruption forms a self-amplifying cycle, and a combination of sleep-promoting and anti-inflammatory therapies may improve clinical outcomes in patients with PAH."

Cardiovascular • CNS Disorders • Heart Failure • Inflammation • Pneumonia • Pulmonary Arterial Hypertension • Respiratory Diseases • Sleep Disorder • IL6

ERO1⁺ macrophage polarization drives hyperlactatemia-aggravated hepatic ischemia-reperfusion injury after liver transplantation (TTS 2026) - "Macrophages were depleted with clodronate liposomes; ERO1 was inhibited with QM295 (10 mg/kg)... Lactate-driven ERO1+ macrophage polarization exacerbates I/R injury via reciprocal hepatocyte–macrophage crosstalk. Pharmacological ERO1 inhibition disrupts this loop and rescues graft injury, identifying ERO1+ macrophages as a promising immunotherapeutic target."

Cardiovascular • Hepatology • Liver Failure • Metabolic Disorders • Reperfusion Injury • Transplantation • CCL3 • ERO1B • FPR2 • IL10 • IL1B • IL1R1 • IL1RAP • LGALS9 • SAA1 • TNFRSF1A

Pseudomonas Aeruginosa Colonization Drives Epithelial-Mesenchymal Transition in Chronic Lung Allograft Dysfunction via Macrophage-Derived THBS-1 (TTS 2026) - "Macrophage-epithelial co-culture, clodronate liposome depletion, THBS-1 neutralizing antibody, and adoptive transfer experiments were performed to validate THBS-1 function... PA colonization induces a functional division of labor among macrophages: ResM initiate recruitment via CCL2, while RecM serve as effector cells secreting THBS-1 to drive EMT. Targeting this macrophage-THBS-1 axis represents a potential therapeutic strategy for infection-associated CLAD."

Fibrosis • Immunology • Infectious Disease • Respiratory Diseases • CCL2 • CDH1 • CDH2 • VIM

Batf2 knockdown ameliorates early-stage hyperoxia-induced BPD-like lung injury and is associated with suppression of GBP5/NF-κB signaling. (PubMed, Int Immunopharmacol) - "Batf2 knockdown alleviates early BPD-like alveolar injury and macrophage-associated inflammatory responses in hyperoxia-exposed neonatal mice. GBP5/NF-κB signaling may partially contribute to Batf2-associated inflammatory regulation, although the cellular and molecular causality of this pathway requires further validation."

Journal • Bronchopulmonary Dysplasia • Inflammation • Pulmonary Disease • Respiratory Diseases • GBP5 • RELA

Pathophysiological Role of Perivascular Macrophages in Blood-Brain Barrier Dysfunction Induced by Cerebral Hypoperfusion in Mice. (PubMed, Neurochem Res) - "Using a mouse model of bilateral carotid artery stenosis (BCAS) to examine cerebral hypoperfusion, the effects of pharmacological depletion of PVM-enriched macrophage populations were examined using clodronate liposomes...These findings suggest that PVM-enriched macrophage populations are involved in early BBB dysfunction following cerebral hypoperfusion, possibly through changes in pericyte-associated vascular integrity, astrocyte activation, and MMP-2/9-related tight junction remodeling. These results provide insight into vascular inflammatory mechanisms that may contribute to hypoperfusion-associated BBB dysfunction and later small vessel pathology."

Journal • Preclinical • Cardiovascular • MMP2 • MMP9

HIF-1α-associated macrophage metabolic reprogramming mediates intestinal injury induced by acrylamide and 5-hydroxymethylfurfural co-exposure. (PubMed, J Hazard Mater) - "Macrophage depletion using clodronate liposomes significantly attenuates this pathology, identifying macrophages as important mediators of the intestinal injury...Pharmacological inhibition or genetic silencing of HIF-1α attenuates metabolic and inflammatory responses, while scavenging mtROS or iNOS inhibition reduces macrophage activation. Collectively, these findings reveal an immune-mediated mechanism underlying AA and HMF co-exposure-induced intestinal injury and highlight macrophage responses as a determinant of contaminant mixture toxicity."

Journal • Inflammation • Metabolic Disorders • HIF1A

Repurposing imeglimin to treat MASH-associated liver fibrosis by targeting the HSC-VNUT-ATP secretory axis: evidence from cell-specific knockout models (EASD 2026) - "Imeglimin is a first-in-class oral antidiabetic agent derived from metformin...Mechanistically, imeglimin (10 µM) directly inhibited intravesicular ATP accumulation and subsequent secretion from HSCs, mimicking the effects of the VNUT inhibitor clodronate... Our findings reveal that imeglimin acts as a "dual-action" agent by improving hepatocellular metabolism and directly suppressing fibrogenesis through inhibition of VNUT-mediated ATP secretion in HSCs. This study provides a novel mechanistic insight into the clinical benefits of imeglimin for treating advanced MASH-associated fibrosis."

Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Spatial synaptic pruning mechanism of NAC microglia in differential regulation of PTSD- and depression-like behaviors. (PubMed, Brain Behav Immun) - "Stress may elicit two regionally heterogeneous microglial subpopulations within NAC: phagocytosis-enhanced and recognition-impaired, which remodel the structure and function of local neural networks by differential pruning of inhibitory synapses, thereby driving the manifestation of PTSD- and depression-like behaviors, separately. These findings deepen our understanding of the neuroinflammatory mechanisms underlying trauma-related psychiatric disorders and identify novel targets for immunomodulation-based targets for transdiagnostic interventions ."

Journal • CNS Disorders • Depression • Immunology • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • CX3CR1 • MERTK

Macrophages Promote Vascular Maturation to Support Tooth Germ Morphogenesis. (PubMed, J Dent Res) - "Functional depletion of macrophages, both in vivo using Cx3cr1-dependent DTA mice and ex vivo with clodronate liposomes, impaired tooth germ growth and morphogenetic progression, accompanied by reduced tooth germ size, abnormal cusp morphology, increased apoptosis, and impaired vascular maturation...Macrophages expressed multiple vascular regulatory factors, including VEGFA, TGF-β, and IL1B, while inhibition of vascular maturation phenocopied the developmental abnormalities caused by macrophage depletion and was associated with attenuated bone morphogenetic protein-associated signaling. Together, these findings identify macrophages as important upstream regulators of tooth germ morphogenesis, acting in part by modulating vascular maturation, and provide new insights into immune-vascular crosstalk during tooth development."

Journal • CX3CR1 • IL1B • TGFB1

The Role of Macrophages in the Immune Response to Peritoneal Infection with Dirofilaria immitis Larvae in the Mongolian Gerbil (Meriones unguiculatus). (PubMed, Pathogens) - "To test whether macrophages mediate larval clearance, peritoneal macrophages were selectively depleted with IP clodronate liposomes (100 µL/10 g body weight; days -4 and -1 relative to infection) before challenge with approximately 40 D. immitis third-stage larvae (L3)...Cytology and flow cytometry confirmed near-complete macrophage depletion, and a significant compensatory neutrophilia was observed in depleted animals (64.5% ± 5.7% vs. 19.6% ± 5.1% in controls; p < 0.0001). These findings establish peritoneal macrophages as the primary innate cellular mediators of D. immitis L3 clearance in a nonpermissive host, providing a validated in vivo framework for mechanistic dissection of filarial host specificity."

Journal • Infectious Disease

Differential roles of resident lung macrophages during control of murine alveolar and airway Mycobacterium abscessus infection. (PubMed, Front Tuberc) - "To understand the role of macrophage subsets in controlling Mabsc infection, clodronate liposomes were administered oropharyngeally to deplete RAMs. RAMs were essential for early control of alveolar Mabsc infection, but depletion of RAMs had no effect on control of Mabsc burden during bead infection. These studies demonstrate that murine Mabsc airway infection induced by obstructing small airways with Mabsc embedded in agar beads generates an immune milieu distinct from that induced by Mabsc infection in alveoli, altering the importance of different macrophage populations for control of infection."

Journal • Preclinical • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • ITGAM • ITGAX

Macrophages orchestrate tail regeneration in lizards Scincella tsinlingensis through spatiotemporal control of immunity, oxidative stress, and myogenesis. (PubMed, Front Cell Dev Biol) - "A tail amputation model was established in S. tsinlingensis, and macrophages were depleted using clodronate liposomes (L-Clodronate)...Their depletion disrupts the early inflammatory switch, impairs blastema formation, and severely limits outgrowth within the 21-day observation period, whereas MMP inhibition only slows regeneration. Macrophages coordinate the immune, myogenic, and matrix remodeling programs essential for successful tissue restoration, highlighting their non-redundant role in reptile regeneration."

Journal • CTSK • CXCL12 • CXCR4 • IL10 • IL6 • MMP2 • MMP9 • MYOD1 • PAX7 • TGFB1 • TNFA

Subchronic Alcohol Exposure Exacerbates Acetaminophen-Induced Acute Liver Injury via Macrophage-Mediated Inflammation and Mitochondrial Dysfunction. (PubMed, Mediators Inflamm) - "Notably, macrophage depletion via clodronate liposomes not only attenuated hepatocyte injury and inflammation induction but also restored the expression of MB/function-related genes, including Pgc-1α, TFAM, and Opa1. These findings suggest macrophage-involved inflammatory amplification may aggravate APAP-induced liver injury, at least in part, by impairing mitochondrial adaptive repair responses."

Journal • Addiction (Opioid and Alcohol) • Hepatology • Inflammation • Liver Failure • Metabolic Disorders • TFAM

The CCL2-CCR2-Ly6c + macrophage axis in PegIFNα-2b therapy for chronic hepatitis B. (PubMed, Immunobiology) - "Our study defines the CCL2-CCR2-Ly6c+ macrophage axis as a critical immunoregulatory pathway in IFN therapy for CHB. This axis coordinates macrophage recruitment, functional differentiation, and cellular crosstalk to mediate the antiviral effects of PegIFNα-2b. These findings may highlight a potential target to refine IFN-driven immunotherapies for CHB treatment."

IO biomarker • Journal • Hepatitis B • Infectious Disease • Inflammation • CCL2 • CCR2 • IFNA1 • IFNAR2

Electroacupuncture regulates macrophage polarization via the TLR4/NF-κB signaling pathway to ameliorate endometrial injury in rats. (PubMed, Cell Signal) - "Notably, macrophage depletion with clodronate liposomes largely abolished the protective effects of EA on endometrial structural repair and functional recovery. Electroacupuncture attenuates IUA associated endometrial injury by suppressing excessive activation of the local TLR4/NF-κB signaling pathway, thereby reprogramming macrophage polarization, mitigating inflammation, inhibiting fibrosis, and promoting organized endometrial regeneration."

Journal • Preclinical • Fibrosis • Immunology • Inflammation • IL1B • IL6 • TLR4 • TNFA

Clodronate Liposome effectively Mitigates Chemically-Induced Retinal Pigment Epithelium Toxicity. (PubMed, Exp Eye Res) - "Given the critical roles of both resident microglia and peripheral macrophages in retinal degenerative diseases, this study systematically evaluated the protective effects of minocycline, PLX3397, and clodronate liposomes in sodium iodate (NaIO3)- and N-methyl-N-nitrosourea (MNU)-induced retinal degeneration models. In contrast, systemic depletion of peripheral macrophages using clodronate liposomes significantly alleviated fundus atrophy, partially preserved visual function, and increased photoreceptor and retinal pigment epithelium (RPE) survival in the NaIO3 model, but conferred no protection in the MNU model. These findings suggest that clodronate liposomes exert model-dependent protection, likely through modulation of peripheral macrophage-mediated RPE toxicity following chemical exposure."

Journal • Ophthalmology

Fibroblast COX-2 Expression in the Development of Progressive Kidney Fibrosis. (PubMed, J Am Soc Nephrol) - "Our findings suggest that fibroblast COX-2 protects against progressive kidney fibrosis, potentially through a regulatory interplay that modulates the surrounding macrophage phenotype during chronic kidney injury."

Journal • Fibrosis • Immunology • Nephrology • Renal Disease • PTGS2 • SPP1

Allogeneic skin transplantation induces transient fibrosis that undergoes spontaneous regression in newts. (PubMed, Inflamm Regen) - "Allogeneic skin transplantation in adult newts induces a distinct response in which non-self tissue is not completely lost and a collagen-rich fibrotic tissue forms transiently and subsequently undergoes resolution. These findings suggest that fibrosis induced under non-self immune activation is not necessarily a terminal state but may represent a dynamically regulated process capable of resolution."

Journal • Fibrosis • Immunology • Transplant Rejection • Transplantation

Tibial cortex transverse transport accelerates diabetic wound healing via systemic mobilization of non-classical monocytes : an animal study. (PubMed, Bone Joint Res) - "Monocyte/macrophage involvement was probed by depleting these cells with clodronate liposomes versus phosphate-buffered saline liposomes...TTT is associated with accelerated diabetic wound repair, accompanied by preferential mobilization of non-classical monocytes and increased M2 macrophage polarization at the wound site. These findings are consistent with a mechanically induced immunomodulatory process that may contribute to improved healing outcomes."

Journal • Diabetes • Type 2 Diabetes Mellitus • CD68 • SIRPA • SPN

Hedyotis diffusa Willd-Scutellaria barbata herbal pair suppresses triple-negative breast cancer metastasis by targeting the tumor-associated macrophage-driven OPN-CD44 signaling axis. (PubMed, Phytomedicine) - "This study demonstrates that the HS herbal pair suppresses TNBC metastasis by remodeling the macrophage functional state and disrupting the signaling axis between OPN and CD44 driven by TAMs. The identification of API as an OPN binding constituent provides a mechanistic basis for further investigation of compounds derived from HS that target macrophage-tumor crosstalk in TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD44 • IL13 • IL4 • MRC1

Macrophages increase in corneal epithelium and stroma after photorefractive keratectomy-like corneal abrasion and amplify ocular pain responses in rats. (PubMed, Exp Eye Res) - "We used subconjunctival liposomal clodronate to deplete macrophages prior to corneal abrasion and found a modest attenuation in acute pain responses, as well as an uncoupling of the relationship between acute pain and the prevalence of CD68+ macrophages at 72 hours. These results suggest that CD68+ macrophages contribute to acute pain after corneal abrasion, but they do not typically make direct contact with corneal nerves."

Journal • Preclinical • Corneal Abrasion • Pain • CD68

Powassan virus infects mouse testes and reveals a protective role for phagocytic cells. (PubMed, bioRxiv) - "Due to macrophages being implicated in driving testicular pathogenesis in Zika virus, a related orthoflavivirus , we depleted phagocytic cells using clodronate liposomes prior to POWV infection and compared to control liposome treated mice...Gene expression analysis revealed a robust antiviral, inflammatory, and chemokine response in the testes that was further amplified following phagocytic-cell depletion. These findings implicate the male reproductive tract as a previously underrecognized target of POWV disease and identify phagocytic cells as key in limiting viral infection of testes in mice."

Journal • Preclinical • CNS Disorders • Infectious Disease • Pain

Benzoylpaeoniflorin regulates macrophage polarization via the RNF31-DPEP2 axis to ameliorate intestinal mucosal barrier damage in ulcerative colitis. (PubMed, Int Immunopharmacol) - "BPF regulates macrophage polarization by modulating the RNF31-DPEP2-NF-κB axis, thereby ameliorating intestinal mucosal barrier damage in UC."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Targeted Protein Degradation • Ulcerative Colitis • RNF31

A preliminary exploration of the role and mechanisms of CD93 in promoting the malignant progression of head and neck squamous cell carcinoma. (PubMed, Front Pharmacol) - "CD93 expression was associated with Wnt/β-catenin activation; CHIR99021 reversed the effects of CD93 knockdown, whereas XAV939 attenuated changes induced by CD93 overexpression...Clodronate liposome-mediated macrophage depletion reduced HSC3-shNC tumor growth and narrowed the difference between HSC3-shNC and HSC3-shCD93 tumors...Docking analysis provides a preliminary structural hypothesis for a potential CD93-LRP6 E1E2 spatial association. CD93 may represent a prognostic biomarker and candidate therapeutic target in HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD93 • MRC1

Embryonic and postnatal macrophages are necessary for proper tooth development and homeostasis. (PubMed, Nat Commun) - "In addition, the short-term pharmacological depletion of macrophages in wildtype adult mice causes striking disintegration of both dentin and enamel in the apical part of continuously-growing teeth, which is restored after withdrawal of clodronate...Overall, our findings reveal essential role of macrophages in the dental development and patterning of both mesenchymal and epithelial tooth compartments. This previously unrecognized role of macrophages in teeth is reminiscent of their function in complex tissue regeneration and requires future studies to dissect precise cellular and molecular mechanisms."

Journal • Bone Marrow Transplantation • Transplantation • CSF1R