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Streptococcal preparation OK-432 is a potent inducer of IL-12 and a T helper cell 1 dominant state
Journal article   Peer reviewed

Streptococcal preparation OK-432 is a potent inducer of IL-12 and a T helper cell 1 dominant state

Toshihiro Fujimoto, Rosemary B Duda, Akos Szilvasi, Xiaohong Chen, Masayoshi Mai and Michael A O'Donnell
The Journal of immunology (1950), Vol.158(12), pp.5619-5626
06/01/1997
DOI: 10.4049/jimmunol.158.12.5619
PMID: 9190909

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Abstract

Streptococcal preparation OK-432 is a bacterial immunopotentiator extensively used in Japan for adjuvant cancer therapy. Using a C57BL/6 mouse model, OK-432 was found to induce multiple cytokines including the Th1 polarizing cytokine IL-12. Expression of IL-12 protein by murine splenocytes was restricted to macrophages and B cells and led to high levels of IFN- gamma production from both CD4 super(+) and CD8 super(+) T cells. Of the Th2 cytokines IL-4 and IL-10, only IL-10 protein was detected and originated primarily from the adherent cell population. Its expression was delayed relative to IL-12. A similar pattern of cytokine induction was observed from human PBMCs. OK-432-driven IFN- gamma production was inhibited by anti-IL-12 Ab, anti-IL-2 Ab, anti-TNF- alpha Ab, and anti-IL-2R alpha Ab, suggesting that IFN- gamma production from Th1 cells is induced by the cooperation action of these cytokines through the IL-2R alpha pathway. When compared with another widely used immunopotentiator bacillus Calmette-Guerin (BCG), OK-432 was a stronger IL-12 and IFN- gamma inducer. Furthermore, the mechanism of IFN- gamma induction by OK-432 differed from BCG in that coincident granulocyte-macrophage CSF and IL-1 expression played little to no role. These results suggest that OK-432 is a potent multicytokine inducer, specifically a strong inducer of IL-12, and that OK-432 may exert its antitumor effect by promoting a Th1-dominant state.
 Streptococcus

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