Regulation of physiological and pathological Th1 and Th2 responses by lactoferrin

In recent years, Lf has gained increasing interest as a result of its protective effects against a variety of diseases. While iron binding and interactions with mammalian receptors and microbial components are the best described mechanisms of action, recent studies have provided evidence that Lf properties may be related to immunoregulatory effects on Th1/Th2 cell activities. In vitro and in vivo experiments show that Lf is able to stimulate the differentiation of T cells from their immature precursors through the induction of the CD4 antigen. Studies performed under nonpathogenic conditions have shown distinct results with regard to the ability of Lf to support the proliferation and differentiation of Th cells into the Th1 or the Th2 phenotype. In addition, Lf plays different roles in diseases by affecting the Th1/Th2 cytokine balance in a manner dependent on the host's immune status. Thus, Lf could cause a Th1 polarization in diseases in which the ability to control infection or tumor relies on a strong Th1 response. Lf may also reduce the Th1 component to limit excessive inflammatory responses. Finally, Lf may provide protection against Th1- or Th2-induced diseases, such as autoimmune or allergic diseases, through correction of the Th1/Th2 imbalance.