IMMUNOPOTENTIATION OF THE GRAFT-VERSUS-HOST REACTION BY LEVAMISOLE

T.B. Stlm, F.3. Persico and M.C. Clark McNeil Pharmaceutical, Spring House, Pennsylvania 19477 U.S.A.

Previously, in a study with levamlsole in the rat graft-versus-host reaction (GVHR), data were presented to support the concept that the directional effect (im~unopotentiatlon vs Immunosuppresslon) of an immunoregulatory drug was dependent on the intensity of the immune response (Stim et al. The Pharmacologist 22:257, 1980). In the present study, levamlsole (5 mg/kg) was administered to Lewis strain donor rats in eight oral dosage regimens (single and multiple). Peripheral blood lymphocytes were harvested after car- diac bleeding and injected into the hind paws of Lewis-Brown Norway F1 (LeBNFI) hybrid rats. Three lymphocyte graft concentrations were used to induce a linear GVHR. Single (day 6) or alternate day (days 2,4,6) dosing with levamiaole of Lewis donors was more efficient in augmentlng the GVHR in LeBNFI recipients than daily dosing over 7 days. In agreement with the previously reported study, the greatest frequency of statistically significant immunoenhancement7bY levamlsole occured in those LeBNFI recipients receiving the smallest number (0.3 x i0 ) of lymphocytes. This confirmation of the influence of GVHR intensity on the immunoregulatory activity of levamisole in this model will facili- tate the study of dose response kinetics.

IMMUNOLOGICAL AND CLINICAL EFFECTS ON CHRONIC LYMPHOCYTIC LEUKAEMIA OF IMMUNOSTIMULANT THERAPY WITH AZIMEXONE.

R.E. Schmidt, D. Boerner, M. Schneider, N. Niederle and I. Stroehmann Medizinische UniversitAtsklinik, 5300 Bonn, Sigmund-Freud-Str. 25, FRG

Azimexone, 2-[2-cyanaziridinyl-(1)]-2-[2-carbamoylaziridinyl-(1)-]propane, has been shown to stimulate the i-zmune system of man and animals. We used this drug with the aim of restoring the deficient immune function in CLL and tried to correlate the in vitro improvement with the in vivo condition of the disease. We treated iO CLL patients with 200 mg azimexone twice weekly i.v. over a period of 6 weeks. Before, during and after therapy we performed skin tests with DNCB, characterised the lymphocytes by determination of SRBC and Sm-Ig, measured Ig serum concentration and determined lymphocyte transformation (LTT) with the polyclonal mitogens PHA, PWM and Con A. Clinically 3 patients showed a slight reduction of liver size, one a reduction of spleen size. None of the patients reported side effects. Five patients converted during treatment period to higher DNCB reaction grades. Five patients showed a better LTT response to PHA during azimexone therapy. There was a significant increase of IgM and IgG during therapy and a drop afterwards. In view of our own results azimexone seems to be mainly a B-cell activator, at least in CLL patients. Further clinical trials to evaluate the action of azimexone in other forms of cancer are necessary.

EFFECT OF INACTIVATED CANDIDA ALBICANS (CA) AND ITS INSOLUBLE GLUCAN GHOST (GG) ON MOUSE

MACROPHAGE-MEDIATED CYTOTOXICITY AND IN VITRO INDUCTION OF CYTOT0XIC T LYMPHOCYTES.

P.Marconi, L.Tissi, L.Scaringi, A.Cassone, A.Vecchiarelli, E.Cenci, F.Bistoni.

• LsDitute of Medical Microbiolo~, University of Perugia and Rome, Italy.

We examined the modulating effect of CA and GG on mouse immune reactivity. Administration

ip to CD2FI mice of a single dose of CA (2xlO 7 organisms/mouse) or GG (i mg/mouse) 7 days

before assay,resulted in an augmentation of lyric activity of spleen cells (SC) and peri-

toneal exudate cells as measured in a 2h hrs 51Cr release assay against MBL-2 tumor cell~

Plastic adherent cell populations were able to mediate such activity suggesting for a ro-

le of macrophages.However, activity was also measurable in the nonadherent cell popula-

tion,suggesting for a possible role of other nonadherent killer cells.Treatment with both

CA or GG administered 16 or 16 and 1 days before assay resulted in a significant diminu-

tion of ability of the mouse SC to develop eytotoxic T lymphocytes in vitro in a 5 aays

mixed lymphocyte culture,as measured against 51Cr-labelled RBL-5 tumor cells.When CA was

administered 19 and h days before assay,the treatment resulted in a significant augmenta-

tion of T cell response.These data indicate that both CA or GG can modulate the meuse im-

mune responsiveness,augmentation or diminution being dependent from the time of adminis- tration and the effector mechanism analyzed. PFCCN N.80.015.05.96 -CNR -ITALY.

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