Vitamin A reduces lung granulomatous inflammation with eosinophilic and neutrophilic infiltration in Sephadex-treated rats

• Published in: European journal of pharmacology 2004-08, Vol.497 (3), p.335-342
• Main Authors: Torii, Akiko, Miyake, Mio, Morishita, Masashi, Ito, Komei, Torii, Shinpei, Sakamoto, Tatsuo
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Bronchoalveolar Lavage Fluid - chemistry; Cell Extracts - chemistry; Chemokine CCL11; Chemokines, CC - biosynthesis; Cytokines - metabolism; Dextrans; DNA-Binding Proteins - metabolism; Dose-Response Relationship, Drug; Eosinophils - pathology; Eotaxin; Granuloma, Respiratory Tract - drug therapy; Granuloma, Respiratory Tract - etiology; Granuloma, Respiratory Tract - pathology; Injections, Subcutaneous; Leukocytes - drug effects; Leukocytes - metabolism; Lung - metabolism; Lung - pathology; Lung granuloma; Male; Medical sciences; Neutrophil Infiltration; NF-kappa B - metabolism; Nuclear factor-κB; Pharmacology. Drug treatments; Pneumonia - drug therapy; Pneumonia - etiology; Pneumonia - pathology; Rats; Rats, Wistar; Sephadex bead; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Vitamin A; Vitamin A - administration & dosage; Vitamin A - pharmacology; Vitamin A - therapeutic use
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.06.056

Vitamin A is known to suppress the activity of the transcription factors, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), as do glucocorticoids. The possibility that vitamin A exerts various anti-inflammatory effects therefore seems likely. Sephadex beads were administered intravenously to anesthesized rats pretreated with a subcutaneous injection of vitamin A (3000, 10,000, or 30,000 IU/kg) or vehicle once daily for 3 days. After 16 h, the leukocyte differential, tumor necrosis factor (TNF)-α and eotaxin, and the DNA-binding activity of NF-κB were measured in bronchoalveolar lavage fluid (BALF). Additionally, lung histology was assessed using preparations stained with May–Giemsa stain. Sephadex beads caused histological granulomatous changes and eosinophilic and neutrophilic infiltration into the lung, and markedly increased cell counts of eosinophils and neutrophils, concentrations of TNF-α and eotaxin, and NF-κB binding to DNA in BALF. Vitamin A significantly inhibited all responses. Vitamin A may inhibit Sephadex-induced lung granulomatous formation, and eosinophilic and neutrophilic infiltration due to its suppression of TNF-α and eotaxin production, and NF-κB activation.