Table 2.
Subgroup meta‐analysis of immunomodulatory effects of lactoferrin and its derived peptides on NF‐κB pathway.
| Author | Year | lactoferrin | Experimental model (exposure dosage/time) | Inflammatory mediator investigated | Major findings |
|---|---|---|---|---|---|
| Crouch | 1992 | Human lactoferrin | The LF model group was exposed to 100 μg/mL hLf and the control group was exposed to 1 μg/mL LPS for 24 h |
Pro‐inflammatory cytokine levels |
IL‐1β (↓) |
| Baltzer | 1996 | Bovine lactoferricin | The LF model group was exposed to 50 μg/mL bLfcin peptide and the control group was exposed to 0.1 μg/mL LPS for 24 h |
Pro‐inflammatory cytokine levels |
IL‐6 (↓) |
| Kruzel | 2002 | Human lactoferrin | The LF model group was injected to 5 mg hLf and the control group was injected to 3·75 × 105 (EU/mouse) LPS for 18 h postinduction |
Pro‐inflammatory cytokine levels |
TNF‐α (↓) IL‐6 (↓) |
| Berlutti | 2006 | Bovine lactoferrin | The LF model group was exposed to 100 μg/mL bLf and the control group was exposed to 1 μg/mL LPS for 4 h |
Pro‐inflammatory cytokine levels |
TNF‐α (↓) IL‐6 (↓) |
| Li | 2009 | Mouse lactoferrin | The LF model group was exposed to 0.2 μg/mL mLF and the control group was exposed to 0.1 μg/mL LPS for 3 h | mRNA levels of IKK‐β | IKK‐β (↓) |
| Ando | 2010 | Human lactoferrin | The LF model group was exposed to 500 μg/mL hLf and the control group was exposed to 75 EU/mL LPS for 24 h |
Pro‐inflammatory cytokine levels |
TNF‐α (↓) NFkB(P65)(↓) |
| Valenti | 2011 | Bovine lactoferrin | The LF model group was exposed to 100 μg/mL bLf and the control group was exposed to 0.1 μg/mL LPS for 3 h |
Pro‐inflammatory cytokine levels |
IL‐1β (↓) IL‐6 (↓) |
| Inubushi | 2012 | Bovine lactoferrin | The LF model group was exposed to 100 μg/mL bLf and the control group was exposed to 0.1 μg/mL LPS for 48 h |
Pro‐inflammatory cytokine levels |
TNF‐α (↓) |
| Inubushi | 2012 | Bovine lactoferrin | The LF model group was exposed to 100 μg/mL bLf and the control group was exposed to 0.1 μg/mL LPS for 4 h | mRNA levels of IKK‐β | IKK‐β (↓) |
| Cutone | 2014 | Bovine lactoferrin | The LF model group was exposed to 100 μg/mL bLf and the control group was exposed to 1 μg/mL LPS for 24 h |
Pro‐inflammatory cytokine levels |
IL‐6 (↓) |
| Frioni | 2014 | Bovine lactoferrin | The LF model group was exposed to 100 μg/mL bLf and the control group was exposed to 1 μg/mL LPS for 24 h |
Pro‐inflammatory cytokine levels |
IL‐1β (↓) IL‐6 (↓) |
| Majka | 2016 | Bovine lactoferrin | The LF model group was exposed to 5000 μg/mL bLf and the control group was exposed to 0.1 μg/mL LPS for 24 h |
Pro‐inflammatory cytokine levels |
TNF‐α (↓) IL‐6 (↓) |
| Rasheed | 2016 | Bovine lactoferrin | The LF model group was exposed to 75 μg/mL bLf and the control group was exposed to nuclear extract for 2 h | NF‐kB(P65) activity | NFkB(P65)(↓) |
| Mantuano | 2016 | Camel lactoferrin | The LF model group was exposed to 0.15 μg/ml CLf and the control group was exposed to 0.1 μg/mL LPS for 8 h | Phosphorylation of IκB‐α | p‐IκB α (↓) |
| Zemankova | 2016 | Human lactoferrin | The LF model group was exposed to 100 μg/mL hLf and the control group was exposed to 1 μg/mL LPS for 6 h | NF‐kB(P65) activity | NFkB(P65)(↓) |
| Zong | 2016 | Human lactoferrin | The LF model group was exposed to 25 μg/mL LFP‐20 peptite and the control group was exposed to 1 μg/mL LPS for 24 h |
mRNA levels of IKK‐β, phosphorylation of IκB‐α, NF‐kB(P65) activity |
IKK‐β (↓) p‐IκB α (↓) NFkB(P65)(↓) |
| Hu | 2017 | Bovine lactoferricin | The LF model group was exposed to 15 μg/mL bLfcin and the control group was exposed to 3 μg/mL LPS for 24 h |
Pro‐inflammatory cytokine levels |
TNF‐α (↓) |
| Daniela | 2017 | Human lactoferrin | The LF model group was exposed to 40 μg/mL hLf and the control group was exposed to 10 μg/mL LPS for 8 h |
Pro‐inflammatory cytokine levels |
TNF‐α (↓) |
| Mohamed | 2018 | Bovine lactoferrin | The LF model group was treated to oral LF capsules (250 mg/day) and the control group was standard therapy without LF for 3 months |
Pro‐inflammatory cytokine levels, NF‐κB (P65) activity |
IL‐1β (↓) IL‐6 (↑) NFkB(P65)(↓) |
| Song | 2019 | Human lactoferrin | The LF model group was exposed to 10 μg/mL LFCA peptite and the control group was exposed to 1 μg/mL LPS for12h | Phosphorylation of IκB‐α | p‐IκB α (↓) |
| Lutaty | 2020 | Bovine lactoferricin | The LF model group was exposed to 10 μm FKD peptite and the control group was exposed to 0.1 μg/mL LPS for 24 h |
Pro‐inflammatory cytokine levels |
TNF‐α (↓) IL‐6 (↓) |
| Zhao | 2020 | Human lactoferricin | The LF model group was exposed to 50 μg/mL hLfcin and the control group was exposed to 0.1 μg/mL LPS for 1 h |
Pro‐inflammatory cytokine levels, phosphorylation of IκB‐α |
TNF‐α (↓) IL‐1β (↓) IL‐6 (↓) p‐IκB α (↓) |
| Yang | 2020 | Human lactoferrin | The LF model group was exposed to 100 mg/kg hLf and the control group was exposed to 1 mg/mL OGD for 4 h | NF‐κB (P65) activity | NFkB(P65)(↓) |
| Li | 2020 | Human lactoferrin | The LF model group was exposed to 100 mg/kg hLf and the control group was exposed to 1 mg/mL OGD for 48 h | NF‐κB (P65) activity | NFkB(P65)(↓) |
| Wright | 2020 | Human lactoferrin | The LF model group was exposed to 100 μg/mL hLf and the control group was exposed to 0.05 μg/mL LPS for 6 h |
Pro‐inflammatory cytokine levels |
TNF‐α (↓) IL‐1β (↓) |
| Nemati | 2021 | Human lactoferrin | The LF model group was exposed to 500 μg/mL hLf and the control group was exposed to 1 μg/mL LPS for 24 h |
Pro‐inflammatory cytokine levels, NF‐κB (P65) activity |
TNF‐α (↓) IL‐6 (↓) NFkB(P65)(↓) |
Abbreviations: bLf, bovine lactoferrin; bLfcin, bovine lactoferricin; cLf, camel lactoferrin; hLf, human lactoferrin; hLfcin, human lactoferricin; mLf, mouse lactoferrin.