Lactoferrin: milking ulcers?

The use of bovine lactoferrin (BL) was recently described triple therapy may help offset the progressively sagging by Di Mario et al. [1] as an ‘add-on’ component to the eradication rates. Of even greater interest may be a clinical 7-day proton pump inhibitor (PPI), claithromycin, study to determine whether simultaneous use of BL with tinidazole-based triple therapy for Helicobacter pylori the PPI triple therapy could significantly inhibit the infection. In this preliminary report 74 patients infected development of clarithromycin resistance during treatment. with H. pylori with or without an active ulcer were Such a trial would necessitate the determination of de-novo randomly assigned to one of three groups: A, patients on and post treatment H. pylori anti-microbial sensitivities; rabeprazole (R), clarithromycin (C) and tinidazole (T), the lack of such a determination is a major limitation of the plus BL; B, RCT for 7 days; and C, RCT for 10 days. The current study. eradication rates were: A, 100% (24/24); B, 76.9% (20/ What mechanisms might be influencing the improved 26); and C, 70.8% (17/24). A significant difference was efficacy of triple therapy when combined with BL? There found between groups A and B ( p50.023) and between are abundant animal studies and a growing number of groups A and C ( p50.022). Results of the complete trial, human studies suggesting that lactoferrin possesses multinow in 150 patients, have become available and are ple functions (Table 1). Lactoferrin is a siderophilin, reported in this issue of the journal [2]. On an ‘intention to comprising a single polypeptide chain folded into two treat’ basis, the results continue to show that BL siglobes with a molecular weight of 90,000 Da [5]. The nificantly improves eradication efficacy of PPI triple structure contains two fucose residues and several Ntherapy. Group A achieved 92% (47/51) eradication acetyl-D-glucosamine residues. It is an iron-binding efficacy while groups B and C reached only 71% (37/52) glycoprotein found in human and bovine milk and in other and 70% (33/47) eradication rates, respectively. Eradicaexternal secretions such as tears [6]. It makes up |0.5–1% tion was significantly higher in group A compared with the or less of whey protein derived from cows milk, whereas other groups ( p50.01). Adverse events were similar human milk may contain up to 15% [5,6]. Its in vitro among all three groups suggesting that BL at a dose of 200 anti-microbial activity, iron binding related antibiotic mg bid is relatively safe and free of side-effects. activity, immuno-modulatory actions, and antioxidant efThese are interesting early results which will need to be fects appear to be but a few of the many characteristics reproduced in other populations with differing H. pylori attributed to BL which could be responsible for its anti-microbial sensitivity profiles. In this Italian populasynergistic effect with PPI triple therapy [1,2,5,6]. Hence, tion, primary clarithromycin resistance is in the order of BL appears ideally suited as an adjuvant therapy on 2% compared with 10% in the USA [3] and over 15% in parts of Australia [4]. Eradication may be dependent upon T able 1 primary anti-microbial resistance and results from one Summary of potential anti-H. pylori effects of BL population group may not apply to another. Conversely, in Effect Reference countries with high or rising clarithromycin resistance, Anti microbial against H. pylori [13] studying the effect of BL on eradication rates is parAntimicrobial effect via sequestering iron from H. pylori [14–16] ticularly important because coupling BL with standard PPI Immuno-modulatory activity [14,15,17,18] Antioxidant effects [19,20] Anti-adhesin activity [21] *Corresponding author. Tel.: 161-2-9713-4011; fax: 161-2-9712Mediates membrane damage and other cell wall effects [22–26] 1675. Macrophage lymphocytes protectant [5] E-mail address: [email protected] (T.J. Borody).