Introduction Materials and Methods Results and Interpretations References

Immunostimulants, primarily targeting natural killer (NK) cells (Lersch et al., 1992; See et al., 1997; Sun et al., 1999), exist in root extracts of the plant Echinacea purpurea. NK cells have been well established throughout the last 20 years, as the first line of defense against developing tumors and virus-infected cells. Extracts from this plant are not only readily commercially available, but have become extremely popular recently for their reported health benefits including abatement of virus-mediated respiratory infections, assorted inflammations (cutaneous and other), tumors, and AIDS (Hill et al., 1996; Lersch et al., 1992; Roesler et al., 1991; Steinmuller et al., 1993; Stimpel et al., 1984; Tragni et al., 1985). There appears, moreover, to be no maximum dose at which this water-soluble herb is toxic in vivo (Lersch et al., 1992; Melchart et al., 1995; Mengs et al., 1991).

The neurohormone, melatonin (MLT), which is produced by the pineal gland almost exclusively during the hours of darkness, coordinates circadian biological rhythms (Mazzoccoli et al., 1997; Nelson and Demas, 1996). Among its many actions, MLT plays an immunoregulatory role (Guerrero and Teiter, 1992; Liebmann et al., 1997). Most of the current popularity of MLT derives from its value in resetting disrupted sleep rhythms resulting from the phenomenon of "jet lag," as well as in the correction of assorted sleep disorders (Pierpaoli and Regelson, 1995). Administration of MLT in humans, hamsters, and mice results in T-cell-mediated functional immunoenhancement in the periphery (Champney et al., 1997; Garcia-Maurino et al., 1997; Nelson and Demas, 1996; Pioli et al., 1993). We have, furthermore, demonstrated (Currier et al., 2000) that NK cells are numerically increased in vivo in the presence of exogenously administered MLT.

As with most herbal products and nutriceuticals, and other agents such as MLT, virtually nothing is known beyond their touted advantages of any long-term, potentially negative effects, or, more importantly, the effect of such agents when taken in combination with other phytochemicals/herbals, hormones, or pharmaceuticals. For example, to date, there exists no quantitative information of the effect on the hemopoietic or immune cell lineages when they are confronted, in vivo, with relatively long-term exposure to a combination of the widely used immunostimulants Echinacea and mela-tonin. A popular concept that "two is better than one," has never been formally tested with respect to Echinacea-derived products and melatonin, under stringent laboratory conditions. Such analyses

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