Freund's adjuvant-induced inflammation: clinical findings and its effect on hepcidin mRNA expression in horses

Abstract

Pesq. Vet. Bras. 34(1):51-56, janeiro 2014 51 hepcidina em equinos.] A hipoferremia observada durante os processos inflamatórios sistêmicos é mediada pela hepcidina. O aumento da expressão da hepcidina é particularmente importante durante a inflamação aguda, por restringir a disponibilidade de ferro necessária para o crescimento de microrganismos patogênicos antes que a imunidade adaptativa ocorra. O objetivo deste estudo foi avaliar os achados clí-nicos e a expressão hepática do RNA mensageiro (RNAm) da hepcidina em cavalos após a indução da inflamação com Adjuvante completo de Freund (FCA). A expressão hepática do RNAm da hepcidina foi determinada em cavalos sadios após duas administrações intramusculares de FCA às 0 h (M0) e 12 h (M12 Hypoferremia observed during systemic inflammatory disorders is regulated by hepcidin. Hepcidin up-regulation is particularly important during acute inflammation, as it restricts the availability of iron, which is necessary for pathogenic microorganism growth before adaptive immunity occurs. The aim of this study was to evaluate the clinical findings and hepatic hepcidin mRNA expression in horses using a Freund's complete adjuvant (FCA) model of inflammation. The expression of hepcidin mRNA in the liver was determined in healthy horses following two intramuscular injections of FCA at 0 h and 12 h. Plasma iron and fibrinogen concentrations were measured at multiple time points between 0 h and 240 h post-FCA injection (PI). Hepcidin mRNA expression was determined by RT-qPCR using liver biopsy samples performed at 0 h (control), 6 h and 18 h PI. The mean plasma fibrinogen level was significantly different from the control values only between 120 and 216 h PI. The mean plasma iron level was significantly lower than the control between 16 and 72 h PI, reaching the lowest levels at 30 h PI (33 % of the initial value), and returned to the reference value from 96 h PI to the end of the experiment. Hepcidin mRNA expression increased at 6 h PI and remained high at 18 h PI. The iron plasma concentration was an earlier indicator of inflammatory processes in horses when compared with fibrinogen and might be useful for the early detection of inflammation in the horse. FCA administration caused the rapid onset of hypoferremia, and this effect was likely the result of up-regulated hepatic hepcidin gene expression. This study emphasizes the importance of hepcidin and iron metabolism during inflammation in horses.

Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects

“…Some AMPs tend to work by sequestration of ions vital for bacterial survival. Hepcidin and Psoriasin reduce the concentration of iron and zinc ions, respectively, and thus restrict the growth of pathogens [ 45 , 46 ].…”

“…During acute inflammation, the increase in levels of iron supports the growth of pathogens, and hepcidin reduces bacterial survival by restricting the availability of iron. In one study, healthy horses were administered with Freund’s complete adjuvant by intramuscular injection at two-time point, namely, 0 h and 12 h. It was observed that 6 h post-infection, hepcidin mRNA increased and remained high until 18 h. The plasma iron concentration decreased significantly between 16 h and 72 h post-infection as compared to control, suggesting the role of hepcidin in the rapid onset of hypoferremia to restrict the availability of iron for the growth of pathogens [ 45 ]. Overexpression of hepcidin in transgenic mice resulted in decreased body iron levels and severe microcytic hypochromic anemia, confirming its role in iron sequestration is central to its activity [ 110 ].…”

Antimicrobial Peptides in Farm animals: An updated review on its diversity, function, mode of action and therapeutic prospects

“…It was observed that 6h post-infection, hepcidin mRNA increased and remained high till 18h. The plasma iron concentration decreased significantly between 16h and 72h post-infection as compared to control, suggesting the role of hepcidin in the rapid onset of hypoferremia to restrict the availability of iron for the growth of pathogens (Oliveira-Filho et al, 2014). Overexpression of hepcidin in transgenic mice resulted in decreased body iron levels and severe microcytic hypochromic anaemia, confirming its role in iron sequestration and central to its activity (Nicolas et al, 2002).…”

“…Some AMPs tend to work by sequestration of ions, which are necessary for bacterial survival. Hepcidin and Psoriasin reduce the concentration of iron and zinc ions, respectively, and thus restrict the growth of pathogens (K. C. Lee and Eckert, 2007;Oliveira-Filho et al, 2014).…”

Whole issue

“…Due to this its feature, FCA has used frequently in animal studies for monitoring changes related to inflammation. In this context, an inflammatory reaction induced by FCA has been shown to occur in rabbits (Fishback et al, 2016), mice (Ferreira et al, 2001;Chillingworth and Donaldson, 2003), horses (Mills et al, 1998;Oliveira-Filho et al, 2014), and dogs (Botrel et al, 1994;Haak et al, 1996). It is reported that the inflammatory reaction may occur with FCA application in sheep as in other animal species (McClure et al, 1991;Badial et al, 2011).…”