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Effect of 2,7-Bis[2-diethylamino)ethoxy]fluoren-9-one dihydrochloride (Tilorone) upon Cell-mediated Immunity in Mice¹

Departments of Medicine and Pharmacology and Section of Orthopedic Surgery, Yale University School of Medicine, New Haven, Connecticut 06510

Tilorone (2,7-bis[2-(diethylamino)ethoxy]fluoren-9-one dihydrochloride) was administered to CD-1 or C57L x A F₁ mice alone or with allogeneic leukemia L1210 cells. Tilorone given alone elicited thymus-dependent lymphocytes in the spleen causing cell-mediated immunity (CMI) comparable to that of lymphocytes exposed to 5 x 10⁴ L1210 cells. This occurred whether Tilorone was administered p.o. or i.p. When administered 24 hr after L1210 cells, an adjuvant effect of Tilorone upon CMI was not demonstrable unless glass-adherent spleen cells were removed before in vitro assay. In groups given Tilorone or L1210 alone, CMI was unchanged after removal of adherent cells. Release of lymphoycte-activating factor by the spleen was unaffected by Tilorone. It is suggested that Tilorone has a moderate direct stimulatory effect upon thymus-dependent lymphocytes but may elicit inhibitory effects mediated by adherent spleen cells (macrophages and/or sticky bursa-dependent lymphocytes) that have also been stimulated by antigen.

¹ Supported by American Cancer Society Grant IC-72 and USPHS Grant CA 13105.

² Instructor in Surgery. Formerly a postdoctoral fellow in Orthopedic Surgery under USPHS Grant AM 05416.

³ Formerly Trainee in Clinical Pharmacology and Chemotherapy under USPHS Grant CA 05318.

⁴ Leukemia Society Scholar; to whom requests for reprints should be addressed, at 333 Cedar Street, New Haven, Conn. 06510.

Received 8/15/73. Accepted 10/31/73.