Differing effects of two iron compounds on experimental arthritis, TNF-alpha levels and immune response in mice.
The effects of ferric-sorbitol-citrate and ferric-citrate on the severity of experimental arthritis, TNF-alpha secretion and the immune status were examined in mice. Arthritis was induced by footpad injection of methylated BSA and intraperitoneal injection of Bordetella pertussis. Joint and footpad swelling were measured weekly by a caliper. TNF-alpha serum levels were measured by ELISA. The immune status was determined by the response of mouse lymphocytes to ConA in vitro and by the antigen-presenting cell assay. Experimental arthritis was aggravated by ferric-citrate, whereas ferric-sorbitol-citrate did not promote it. If applied to normal (non-arthritic) mice three times a week for 4 weeks, ferric-sorbitol-citrate stimulated isolated splenocytes to increase production of TNF-alpha, the function of antigen-presenting cells and lymphocyte proliferation in response to ConA in vitro. TNF-alpha production by cultured splenocytes was also stimulated. In mice with antigen-induced arthritis, iron compounds did not additionally stimulate TNF-alpha production. Thus, we have shown that ferric-sorbitol-citrate stimulated TNF-alpha production, antigen-presenting cell activity and cellular immune response. Development of antigen-induced arthritis and TNF-alpha production in arthritic mice were not stimulated.
Poljak-Blazi
Marija
M
Division of Molecular Medicine, Rudjer Bosković Institute, POB 180, Bijenicka 54, 10002 Zagreb, Croatia. marija@rudjer.irb.hr
Hrvacić
Boska
B
Zupanović
Zeljko
Z
Hadzija
Mirko
M
Stanić
Barbara
B
Polancec
Denis
D
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019343:Citric Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D007273:Injections, Intramuscular; D058085:Iron Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D013012:Sorbitol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D004338:Drug Combinations; D005290:Ferric Compounds; D058085:Iron Compounds; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine; D019343:Citric Acid; D013012:Sorbitol; C025314:ferric citrate