Inhibition of in vitro LAK generation by OK-432

The present study was designed to investigate the in vitro effect of OK-432 on interleukin-2-(IL-2) induced lymphokine activated killer (LAK) generation, and especially to test whether OK-432 can substitute for IL-2 or act in synergism with IL-2 for activation of cytotoxic lymphocytes. Surprisingly, our results showed that the addition of OK-432 to 4-day LAK activation cultures significantly inhibited both the generation of cytotoxic effectors to the natural killer (NK) resistant Daudi cell line and the proliferative responses of lymphocytes in a dose dependent manner. The inhibition of activation was total at 0.5 KE/ml of OK-432, a dose which was still effective in augmenting NK activity against K562. The addition of penicillin G potassium (PCGk), which is contained in OK-432 at a concentration of 134,700 units/mg of dried cocci, to the LAK culture system also inhibited LAK generation at equivalent concentrations as contained in the OK-432 preparation. This inhibition of LAK generation by OK-432 was significantly eliminated by dialysis of OK-432. These results indicated that the inhibition of LAK generation was partly due to PCGk contained in the OK-432 preparation, and that OK-432 did not act synergistically with IL-2 in standard LAK activation systems.

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