Spirulina platensis is a cyanobacterial species that is surmised to potentiate the immune system leading to suppression of
cancer development and viral infection. Here, we identified the molecular mechanism of the human immune potentiating
capacity of Spirulina by analyzing blood cells of volunteers with pre and post oral administration of hot water extract of
Spirulina. NK functions represented by IFN gamma production and cytolysis were enhanced after administration of Spirulina in
>50% subjects. IFN gamma was produced in an IL-12/IL-18-dependent fashion. In vitro stimulation of blood cells with BCG
cell wall skeleton (CWS) allowed more potent IL-12 p40 production in cells from volunteers given Spirulina than in cells
without pre-exposure to Spirulina. As BCG–CWS serves as a ligand for Toll-like receptor (TLR) 2 and 4 to raise the maturation
stage of monocytes/macrophages, Spirulina may be involved in the signaling responses through Toll in blood cells even when
orally administered. These observations indicated that in humans Spirulina acts directly on myeloid lineages and either directly
or indirectly on NK cells. The presence of co-operative IL-12 and IL-18 is critically important for NK-mediated IFN gamma
production. D 2002 Elsevier Science B.V. All rights reserved.