Differing effects of two iron compounds on experimental arthritis, TNF-α levels and immune response in mice

The effects of ferric-sorbitol-citrate and ferric-citrate on the severity of experimental arthritis, TNF-α 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-α 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-α, the function of antigen-presenting cells and lymphocyte proliferation in response to ConA in vitro. TNF-α production by cultured splenocytes was also stimulated. In mice with antigen-induced arthritis, iron compounds did not additionally stimulate TNF-α production. Thus, we have shown that ferric-sorbitol-citrate stimulated TNF-α production, antigen-presenting cell activity and cellular immune response. Development of antigen-induced arthritis and TNF-α production in arthritic mice were not stimulated.