Conjunctival Injection Reduction in Patients with Atopic Keratoconjunctivitis Due to Synergic Effect of Bovine Enteric-Coated Lactoferrin in 0.1% Tacrolimus Ophthalmic Suspension

Abstract

Lactoferrin (LF), a multifunctional glycoprotein found in mammalian milk, is reported to have immunoregulatory effects. The present study aimed to evaluate whether enteric-coated LF (eLF) could improve symptoms in patients with atopic keratoconjunctivitis (AKC). This randomized double-blind placebo-controlled single-center trial comprised Japanese patients (n = 20; aged 22–60 years) with AKC. Patients treated with 0.1% tacrolimus ophthalmic suspension (TALYMUS®) were administered eLF (400 mg/d of bovine LF) or placebo tablets for 12 weeks. Conjunctival injection was examined, papillae formation in the palpebral conjunctiva was evaluated, and corneal fluorescein score, itchy sensation in end-point itching scale, and serum allergic parameters were assessed. Conjunctival injection was significantly reduced in the LF group than in the placebo group (p = 0.0017, Mann–Whitney U-test). Papillae formation in the palpebral conjunctiva showed a statistical decrease in the LF group than in the placebo group (p = 0.010, unpaired T-test). LF combined with TALYMUS® could be a promising treatment strategy to mitigate AKC.

Effect of Lactoferrin Supplementation on Inflammation, Immune Function, and Prevention of Respiratory Tract Infections in Humans: A Systematic Review and Meta-analysis

“…In adults, inflammation (IL-6) was attenuated when Lf was administered alone in doses of 200 mg/d in pregnant and nonpregnant females with iron homeostasis disorders ( 43 , 45–47 ), although doses of only 32 mg/d given in combination with whey protein were also effective in reducing CRP, TNF-α, and IL-6 in T2D ( 55 ). Lf doses >200 mg/d, given either alone or in combination with other compounds, were effective in reducing systemic inflammation outcomes in some ( 41 ), but not all ( 35 , 40 , 48 , 53 ), trials. Doses <200 mg/d were not effective in some combinations in adults ( 57 ) and children ( 54 ).…”

“…The subject population of most trials in adults was healthy subjects ( n = 9, 36%), followed by pregnant and nonpregnant females with hereditary thrombophilia (HT) ( n = 2, 8%) or iron deficiency (ID) ( n = 2, 8%), with 1 trial each in type 2 diabetes (T2D), polycystic ovarian syndrome (PCOS), bedridden neurological patients, atopic dermatitis (AD), patients with colonic polyps, periodontal disease, and atopic keratoconjunctivitis (AK). All trials used bLf in doses ranging from 32.4 mg/d to 3 g/d (median: 225 mg/d), delivered either alone [total, n = 14, 56%; tablet, n = 6 ( 35–40 ); capsule, n = 7 ( 41–47 ); powder, n = 1 ( 48 )], or in combination with other ingredients [enteral/infant feeding formula, n = 6 ( 49–54 ); whey protein, n = 2 ( 55 , 56 ); synbiotic, n = 2 ( 57 , 58 ); and myo-inositol, n = 1 ( 59 )]. The comparators/controls included inert placebo formulations ( n = 5), matched control feeding formula ( n = 5), calcium phosphate ( n = 4), a different dose of bLf ( n = 3), routine care (ferrous sulfate, n = 2), synbiotic ( n = 1), and prebiotic ( n = 1), while 3 trials were noncontrolled.…”

“…The intervention duration ranged from 1 to 60 wk (median: 12 wk). The effects of bLf supplementation on systemic inflammatory biomarker outcomes were measured in 13 trials (52%) ( 35 , 40 , 41 , 43 , 45–48 , 53–55 , 57 , 59 ) ( Table 1 ), 8 trials (32%) ( 36–39 , 42 , 44 , 48 , 53 ) measured immune function outcomes ( Table 2 ), and 10 trials (40%) ( 39 , 42 , 49–54 , 56 , 58 ) reported on RTI outcomes ( Table 3 ). Airway inflammation was not measured as an outcome in any included trials.…”

“…Serum IgE was measured in 2 trials, and did not change following either bLf 400 mg/d for 12 wk in subjects with AK ( 35 ) or 250 mg for 56 d in participants with AD ( 41 ).…”

“…Other inflammatory biomarkers that were not affected by bLf supplementation included serum eosinophil cationic protein (ECP) ( 35 ) after 400 mg/d for 12 wk in subjects with AK and plasma IL-16 and IL-18 after 150 mg/d for 21 d in male athletes ( 57 ).…”