It is not known whether the parent carotenoids or their metabolites are the active factors (Hanusch et al., 1995), nor is it known whether carotenoids influence this communication process in vivo. More study is needed to ascertain whether carotenoids play a direct role in cell-cell communication and, if so, what health outcomes are influenced by this action.

There has been great interest in the potential role of carotenoids in enhancement of the immune response. Children with vitamin A deficiency suffer from compromised immunity and have difficulty protecting themselves from infections. It is important to remember, however, that studies conducted with provitamin A carotenoids may yield results that are attributable to the conversion of carotenoids to vitamin A or other retinoids, not to the effects of the intact carotenoid.

Santos et al. (1996) showed that long-term β-carotene supplementation enhanced natural killer cell activity in men 65 to 86 years of age, but not in men 51 to 64 years of age; enhancement by β-carotene in this age group was confirmed in a subsequent study (Santos et al., 1998). Hughes et al. (1997) evaluated mechanisms by which β-carotene might enable immune cells to act more efficiently. Subjects were supplemented for 26 days with either 15 mg of β-carotene or a placebo. Subjects receiving the β-carotene treatment had increases in expression of adhesion molecules by monocytes, in ex vivo secretion of tumor necrosis factor-α, and in the percentage of monocytes expressing major histocompatibility complex II, a cell surface molecule responsible for presenting antigen to T-helper cells.

Other immunological effects that carotenoids are reported to increase are lymphocyte response to mitogens (Kramer and Burri, 1997) and total white blood cells and helper T cells in human immunodeficiency virus-infected humans (Coodley et al., 1993). Whether these and the other effects noted are specific to carotenoids and are important in overall immunity is not confirmed. Therefore the usefulness of these as markers for disease has yet to be established.

A vast number of observational studies, including both case-control and cohort studies, of carotenoids and chronic disease risk have