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Enhancement of Natural Killer Cytotoxicity by cis-Diamminedichloroplatinum (II) in Vivo and in Vitro¹

Department of Medicine, Veterans Administration-Wadsworth-UCLA Medical Center [A.K.L.], and Department of Microbiology and Immunology, UCLA Medical School [D.P.], Los Angeles, California 90024

To investigate the immunomodulating properties of cis-diamminedichloroplatinum (II) (CDDP), we studied the drug's effects on natural killer (NK) lymphocyte cytotoxicity. i.p. injections of CDDP (2–6 mg/kg) into adult mice significantly enhanced cytolysis of YAC-1 and K562 targets mediated by peritoneal and spleen cells. Lysis of the NK-resistant targets P815, EL-4, MOT, and RAJI was not increased, nor was the lysis of a YAC variant which had been specifically rendered resistant to NK lysis. Activated cytotoxicity was first noted 24 h after injection and returned to baseline by 7 days. Although i.p. injection enhanced peritoneal and spleen cell lysis, i.v. injection only activated spleen cells. Two analogues of CDDP, carbo- and iproplatin, effectively enhanced NK activity, but transplatin had no effect. Activated effector cells were non-adherent to nylon wool and serum-coated plates; they co-separated with lymphocytes on Percoll gradients, and they expressed asialo GM₁ determinants. Incubation of targets with CDDP for 1 or 18 h significantly increased their sensitivity to lysis by normal murine spleen cells. These data indicate that CDDP has potent effects on NK cytotoxicity.

¹ Supported by USPHS grant 1R01 CA37184-01 A1, awarded by the National Cancer Institute, Department of Health and Human Services, and research funds of the Veteran's Administration.

² To whom requests for reprints should be addressed, at Veterans Administration Wadsworth Hospital, 691/111H, Wilshire and Sawtelle Blvds., Los Angeles, CA 90073.

Received 6/28/85. Revised 10/ 1/85. Accepted 10/ 2/85.