potassium-permanganate and Inflammation

RANTES (regulated on activation, normal T cell-expressed and secreted) is a CC chemokine appearing to be involved in the recruitment of leukocytes at inflammation sites. RANTES is produced by CD8(+) T cells, epithelial cells, fibroblasts, and platelets. It acts in vitro in leukocyte activation and human immunodeficiency virus suppression, but its role in vivo is still uncertain. In our study, we established the involvement of RANTES in an in vivo model of chronic inflammation induced by potassium permanganate, leading to calcified granulomas. In our rat model, RANTES expression (mRNA and protein) was significantly upregulated in granulomatous tissue; RANTES expression was further increased upon i.p. injection of lipopolysaccharide (LPS), while it was kept at basal levels by dexamethasone (Dex) given 18 hours before sacrifice. LPS and Dex increased and decreased, respectively, the recruitment of mononuclear cells in granulomatous tissue compared with control granulomas from phosphate-buffered saline (PBS)-treated animals. In granuloma tissue, levels of RANTES were higher in LPS-treated rats and lower in the Dex group compared to controls. RANTES was also found in the conditioned medium of granuloma tissue from treated (LPS or Dex) and untreated (PBS) rats. When LPS was added in vitro for 18 hours, RANTES was further increased, except in the Dex group (P > 0.05). On serum analysis, RANTES levels were higher in the LPS group and lower in the Dex group compared to controls. This study shows for the first time that RANTES is produced in vivo in chronic, experimental inflammatory states, an effect increased by LPS and inhibited by Dex.

Topics: Animals; Anti-Inflammatory Agents; Chemokine CCL5; Chronic Disease; Dexamethasone; Disease Models, Animal; Gene Expression Regulation; Granuloma; Inflammation; Lipopolysaccharides; Potassium Permanganate; Rats; Rats, Wistar; RNA, Messenger

4-Deoxypyridoxine (4-DPD) is a potent antagonist of Vitamin B6 coenzyme which inhibits IL-1, lymphocyte proliferation and has demonstrated that tolerance to skin grafts can be induced by administering splenic cells to pyridoxine-deficient mice. Chronic inflammation induced by dorsal injections of 200 microliters of a 1:40 saturated crystal solution of potassium permanganate (KMnO4) in mice treated or untreated with 4-DPD (400 micrograms/dose), has been investigated. After 7 days all mice developed a subcutaneous granulomatous tissue indicative of a chronic inflammatory response, at the site of injection. KMnO4-treated mice injected intraperitoneally with 4-DPD (400 micrograms/dose) on 5 consecutive days (the first at the same time of induction of the granuloma) show a significant decrease in size and weight of granuloma when compared to mice not treated with 4-DPD (Controls). In addition, in all mice treated with 4-DPD there was a strong inhibition of TNF alpha in serum (P < 0.01) and in supernatant fluids (P < 0.05) from minced granuloma, while IL-6 was inhibited in the supernatant fluids (P < 0.05) of minced granulomas but was not detected in the serum of treated and untreated mice. In this study we show for the first time the antiinflammatory effect of 4-DPD on chronic inflammation and the inhibitory effect of TNF and IL-6 generation in supernatant fluids from minced granulomas.

Topics: Animals; Granuloma; Inflammation; Interleukin-6; Lymphocytes; Mice; Potassium Permanganate; Pyridoxine; Tumor Necrosis Factor-alpha

Topics: Animals; Anti-Inflammatory Agents; Dexamethasone; Drug Evaluation, Preclinical; Inflammation; Male; Potassium Permanganate; Rats

Topics: Animals; Ascorbic Acid; Cobalt; Copper; Cysteine; Dactinomycin; Deferoxamine; Dinitrophenols; Edetic Acid; Fatty Liver; Fluorides; Fructose; Glucose; Glutathione; Hemochromatosis; Inflammation; Iodoacetates; Iron; Lipotropic Agents; Liver Cirrhosis; Lung; Macrophages; Microscopy, Electron; Potassium Permanganate; Protein Biosynthesis; Puromycin; Rabbits; RNA; Saponins; Sucrose; Surface-Active Agents; Transferrin; Trypsin

Topics: Anaphylaxis; Animals; Calcinosis; Calciphylaxis; Connective Tissue; Dihydrotachysterol; Edema; Female; Foot Diseases; Formaldehyde; Hemorrhage; Inflammation; Ischemia; Lead; Necrosis; Pharmacology; Potassium Permanganate; Rats; Serotonin; Stress, Physiological; Thrombosis