Putative immunoregulatory factors

Glycoproteins from human colostrum have an enhancing effect on T-cell proliferation at low concentrations but an inhibitory effect at high concentrations (Mincheva-Nilsson et al., 1990). The biological significance of this in vitro phenomenon is obscure as long as the active factors remain unidentified. One inhibitory mechanism of breast milk was suggested to be down-regulation of IL-2 production (Hooton et al., 1991) and multimeric colostral a-lactalbumin was shown to induce apoptosis in lymphocytes (Hakansson et al., 1995). Conversely, the stimulatory effect of milk on T-cells was tentatively ascribed to lactoferrin (Mincheva-Nilsson et al., 1990), but great confusion exists about the possible immunoregulatory properties of this protein (Brock, 1995).

Several studies have reported that unfractionated supernatants of breast milk cell cultures preferentially stimulate IgA production by peripheral blood lymphocytes (Slade and Schwartz, 1987). An explanation for this effect may be the various cytokines that are secreted by stimulated milk macrophages (Wold and Hanson, 1994). The same soluble cytokines are found in breast milk (Goldman, 1993), and the presence of TGF-ß, IL-6 and IL-10 is of particular interest for the development and differentiation of IgA-producing cells (Brandtzaeg et al., 1999a). Evidence to this end has been provided for IL-6 (Saito et al., 1991), as well as for IL-10 and TGF-ß (Böttcher et al., 2001), by relating the levels of cytokines in breast milk to salivary IgA concentrations in breast-fed children. Even if these cytokines are unable to survive the passage through the gastrointestinal tract, they may be released locally from milk macrophages in the neonatal gut and promote the development of a balanced mucosal immune system, thus contributing to a subsequent responder pheno-type compatible with health. In this context, the balance between the immuno-suppressive IL-10 and the Th2-promoting IL-4 in breast milk (Böttcher et al., 2000) might be of particular significance. Also, the high levels of soluble Fas (CD95) could be important, because this protein might protect the intestinal epithelial barrier against apoptosis and favour tolerance induction (Srivastava and Srivastava, 1999).

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