Effect of Ferric Sorbitol Citrate (FSC) Administration on NF‐κB in Macrophages and Spleen Cells of Rats

Abstract

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.

Acute immunomodulatory effects of iron polyisomaltosate in rats

“…We have found time-dependent effects of acute iron polyisomaltosate administration on serum iron, IL-6 and 5-HT concentrations, respiratory burst of granulocytes, activation of p65, p50 and RelB subunits of NF-kB in subcellular fraction of peritoneal macrophages and spleen cells. Part of these results are in line with our previous data showing the immunomodulatory effects of another iron compound, FSC (Fe 3+ ) in mice (Poljak-Blazi et al, 2003) and in rats (Bosnjak et al, 2004). Significant increase in serum iron concentration was observed as early as 1.5 h after i.p.…”

“…In addition FSC acts as a modulator of the immune system, throughout the activation of the NF-kB transcription factors in peritoneal macrophages and spleen cells in rats (Bosnjak et al, 2004). Therefore, our previous studies (Poljak-Blazi et al, 2003;Bosnjak et al, 2004) elucidated the effects of anti-anaemic iron Fe 3+ compound Jectofer (FSC complex), while the present study investigated the effects of the anti-anaemic iron Fe 3+ compound, Ferrum (iron polyisomaltosate complex). Both compounds contain iron in Fe 3+ form, but differ in carbohydrates ingredients.…”

“…To exclude possible gender differences in the iron induced changes in IL-6 and 5-HT concentration, neutrophil activity, and NF-kB activation in peritoneal macrophages and spleen cells, the previous (Bosnjak et al, 2004) and present study on the immunomodulatory effect of the iron compounds were performed in female rats.…”

“…The activation of NF-kB in macrophages also resulted in secretion of cytokines and TNF-a (Schwertschlag et al, 1999). Recently, we have shown that iron compound ferric-sorbitol citrate (FSC) stimulated TNF-a production in mice (Poljak-Blazi et al, 2003) and rats (Bosnjak et al, 2004). In addition FSC acts as a modulator of the immune system, throughout the activation of the NF-kB transcription factors in peritoneal macrophages and spleen cells in rats (Bosnjak et al, 2004).…”

“…Recently, we have shown that iron compound ferric-sorbitol citrate (FSC) stimulated TNF-a production in mice (Poljak-Blazi et al, 2003) and rats (Bosnjak et al, 2004). In addition FSC acts as a modulator of the immune system, throughout the activation of the NF-kB transcription factors in peritoneal macrophages and spleen cells in rats (Bosnjak et al, 2004). Therefore, our previous studies (Poljak-Blazi et al, 2003;Bosnjak et al, 2004) elucidated the effects of anti-anaemic iron Fe 3+ compound Jectofer (FSC complex), while the present study investigated the effects of the anti-anaemic iron Fe 3+ compound, Ferrum (iron polyisomaltosate complex).…”