Background Lactoferrin is a multifunctional immunoregulatory protein, stored in specific granules of neutrophil granulocytes, from which it is released following cell activation. While the biochemical characterisation of lactoferrin as an iron-binding protein has been well described, its physiological role in inflammation remains undefined. Although lactoferrin was proven to exert certain antiinflammatory effects, there is a paucity of data concerning the possibility of administrating lactoferrin as an anti-inflammatory agent in rheumatoid arthritis.
Objectives To evaluate the anti-inflammatory properties of lactoferrin in treatment of adjuvant arthritis ? an adequate model of rheumatoid arthritis.
Methods Adjuvant arthritis was induced in Lewis rats by subplantar inoculation of a complete Freund?s adjuvant. Human milk-derived lactoferrin was administered intravenously in the acute phase (8th day after adjuvant inoculation), and in the chronic phase of adjuvant arthritis (29–31 days).
Results The development of adjuvant arthritis in rats was characterised by hind paws swelling and hyperthermia, weight loss, increased white blood cell count and erythrocyte sedimentation rate, an increased level of serum elastase. In approximately 50% of rats a generalisation of inflammation with involvement of intact joints was observed. Treatment with low doses of lactoferrin (3–18 mg/kg) in the acute phase of adjuvant arthritis did not change the course of the disease, while higher doses of lactoferrin (30–60 mg/kg) caused a certain suppression of the inflammatory process, although it was not stable and lasted for only 2 weeks. The serum level of elastase remained unchanged. The administration of lactoferrin in the chronic phase of adjuvant arthritis resulted in a steady suppression of the inflammatory process (decreased hind paws swelling and local temperature, white blood cell count and erythrocyte sedimentation rate, an increase in weight gaining and a decrease in serum elastase level), which lasted until the end of experiment (day 50). This effect was achieved with lower doses of the drug (9 mg/kg), though its strength was dose-dependent. The maximal suppression of adjuvant arthritis was obtained with the repeated injections of lactoferrin (5 injections every other day with total dose of 60 mg/kg) in the chronic phase of adjuvant arthritis (days 23–31). In these rats the serum concentration of elastase was reduced down to normal level and the rate of generalisation was less than 8%.
Conclusion Lactoferrin is a potent anti-inflammatory agent effective in treatment of adjuvant arthritis in rats. The maximal suppression of the inflammatory process is obtained in the chronic phase of adjuvant arthritis.
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