Vitamin A reduces lung granulomatous inflammation with eosinophilic and neutrophilic infiltration in Sephadex-treated rats.
Vitamin A is known to suppress the activity of the transcription factors, nuclear factor-kappaB (NF-kappaB) 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)-alpha and eotaxin, and the DNA-binding activity of NF-kappaB 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-alpha and eotaxin, and NF-kappaB 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-alpha and eotaxin production, and NF-kappaB activation.
Torii
Akiko
A
Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Miyake
Mio
M
Morishita
Masashi
M
Ito
Komei
K
Torii
Shinpei
S
Sakamoto
Tatsuo
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002457:Cell Extracts / Q000737:chemistry; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003911:Dextrans; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000473:pathology*; D015769:Granuloma, Respiratory Tract / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007279:Injections, Subcutaneous; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C515458:Ccl11 protein, rat; D002457:Cell Extracts; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D004268:DNA-Binding Proteins; D003911:Dextrans; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014801:Vitamin A; C025614:sephadex