Lactoferrin and FIV
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Bovine lactoferrin has many potential virtues as a supplement for FIV+ cats. An iron-binding protein of the transferrin family produced by humans and other mammals, lactoferrin is an important part of the immune system found in milk, saliva, tears, and intestinal and respiratory secretions. It has a
particular affinity for lymphatic and mucosal tissue, where it plays an important role in protection from a number of bacterial, viral, parasitic, and cancerous diseases. Lactoferrin supplements are derived from cows, and, strangely, bovine lactoferrin, which shares about 86% amino acid sequencing with its native human counterpart, has, in some cases, shown more protective action for people . Lactoferrin occurs in vivo in four forms, including an iron-saturated holo-form and an iron-depleted apo-form, both of which are available as supplements. Various claims are made for each, and individual forms of lactoferrin (including the lactoferrin-derived peptide lactoferricin) have shown strikingly different levels of activity in different experimental situations.
Several studies have shown that lactoferrin inhibits all three enzymes needed by HIV to reproduce  and lowers viral counts in HIV-infected children , so there is a good chance that it has some inhibiting action against FIV. Recent studies have also shown that it blocks binding of HIV to a type of immune cell (dendritic cells) that spreads infection to the CD4+ T cells whose loss and dysfunction is directly related to immunedeficiency . This same cell type has been been implicated in FIV infection of feline CD4+ T cells . Studies have shown that counts of several important immune cells are higher in HIV-infected people when supplemented with bovine lactoferrin . In a 2002 study with mice, lactoferrin reconstituted immune responsiveness (delayed hypersensitivity and lymphoproliferative) following administration of cyclophosphomide, a powerful immunosuppressive agent used in cancer therapy. "LF also caused substantial restoration of the percentage of the lymphocyte population in circulating blood" and "strongly elevated the pool of CD3+ T cells in normal and CP-immunocompromised mice and CD4+ T cell content. . . .we showed for the first time that lactoferrin, given orally to CP-immunosuppressed mice, could reconstitute a T-cell mediated immune response by renewal of the T cell pool" .
Lactoferrin works, in part, by stimulating release of anti-inflammatory signalling proteins ("cytokines") that travel throughout the body. The
anti-inflammatory action is related to lactoferrin's ability to inhibit a number of cytokines that normally direct the immune system to react in an inflammatory way. Lactoferrin has been shown to inhibit ongoing expression of the inflammatory acute-phase proteins (APP) IL-1, IL-6, and TNF-α . Because retroviral infection causes chronic hyperactivation of the "first-alert" acute-phase response , this ability is of particular importance. Another recent in vitro study using blood samples from both asymptomatic and symptomatic FIV+ cats found that "bLF [bovine lactoferrin] has a protective effect on activated cells by inhibition of apoptosis [programmed cell death] and modulation of proliferation and cell cycle progression" The study showed that lactoferrin is immunomodulatory rather than immunosuppressive because it resets the level of cytokine expression to or near that characteristic of uninfected cats, without affecting the ability of cells to normally express them (as, for instance, steroids would). And the immunomodulating action was stronger in symptomatic (ARC) than in asymptomatic (AC) cats. "We observed that addition of bLF inhibited . . . increase of IFN-γ and IL-2 expression in PBMC [peripheral blood mononuclear cells] from the ARC group. . . . Bovine LF did not affect the spontaneous expression of IL-1β, TNF-α and IL-12 p40. . . ” . Because Interleukens-2 and -12 are necessary for normal T-cell recruitment and maturation, it is important that they not be suppressed below normal levels.
What kinds of potentially FIV-related conditions might lactoferrin be of benefit for? In several studies, direct application of lactoferrin to oral tissue of cats lessened the effects of stomatitis , although it can also be added to food. Additionally, native lactoferrin is produced by probiotics, and it is reasonable to suppose that supplementation has some beneficial activity for inflammatory conditions of the gut . It gets better. Bovine Lactoferrin has also been shown effective against bacterial infections and parasites such as toxoplasmosis , in part through its ability to deprive pathogens of the iron they need in order to replicate  and in part through its ability to bind lipopolysaccharides (LPS) in the cell membranes of gram-negative bacteria . It is also active against a number of
viruses. The antiviral function of lactoferrin, originally attributed to its iron deprivation capability, may be due to a specific binding to heparin sulfate, a necessary constituent of cell-membrane receptors used by some enveloped viruses . “The greater inhibitory activity of iron-saturated forms may be due to an increased affinity for viral cell receptors as result of the conformational changes induced after iron-binding” . In discrete studies, lactoferrin has been shown to inhibit replication of both feline herpes virus  and calici virus ; in a small in vivo study, its sister transferrin, ovotransferrin, which has a biochemical action very similar to lactoferrin's, has shown an ability to both prevent and cure feline upper respiratory infections in FIV+ cats . Finally, lactoferrin has shown an ability to inhibit metastisis of a variety of forms of cancer  and to potentiate other cancer treatments by enhancement of T and NK cell activity .
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