RESUMO
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.
Assuntos
Artrite Experimental/tratamento farmacológico , Autoimunidade/imunologia , Compostos de Ferro/uso terapêutico , Fator de Necrose Tumoral alfa/imunologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Autoimunidade/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Ácido Cítrico/administração & dosagem , Ácido Cítrico/farmacocinética , Ácido Cítrico/uso terapêutico , Modelos Animais de Doenças , Esquema de Medicação , Combinação de Medicamentos , Compostos Férricos/administração & dosagem , Compostos Férricos/efeitos adversos , Compostos Férricos/farmacocinética , Injeções Intramusculares , Compostos de Ferro/administração & dosagem , Compostos de Ferro/química , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/imunologia , Sorbitol/administração & dosagem , Sorbitol/farmacocinética , Sorbitol/uso terapêutico , Baço/citologia , Baço/efeitos dos fármacos , Timo/citologia , Timo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Interaction of iron metabolism and the immune system is complex and pathological changes in one system affect the other. Ferric sorbitol citrate (FSC), non-toxic compound of ferric ions with sorbitol and citrate. has immunomodulatory effect in treated mice. We investigated an effect of FSC on NF-kappaB expression/activation in peritoneal macrophages and spleen cells of rats. TNF-alpha concentrations in sera of control and FSC intraperitoneal (i.p.) treated Wistar rats were measured by ELISA. Furthermore, peritoneal macrophages (PM) were counted and splenocytes were isolated. PM and splenocytes were lysed and their cytoplasmic and nuclear fractions were separated by centrifugation. The influence of FSC on NF-kappaB expression and/or activity as well as expression of its inhibitor IkappaB-alpha was measured by Western blot. 1.5 and three hours after FSC treatment TNF-alpha level in sera was significantly (p < or = 0.05) increased. Activation of transcription factor NF-kappaB in PM was detected three hours after treatment, followed by significant increment in PM number. In splenocytes NF-kappaB was activated six and 48 hours after FSC application. The results indicate that, after i.p. application, FSC acts as a modulator of the immune system activating NF-kappaB in PM. PM consequently secrete TNF-alpha that activates NF-kappaB in splenocytes.