- Email: [email protected]
In vitro effects of ranitidine on human lymphocyte functions
369
EFFECT OF RU 41740 ON THE IN VITRO MA~'JRATION OF HUMAN B CRIJS.
48
A.DurandF*, P.Smets**, R.Zalisz** and C.Griscelli*. * Inserm U 132 H6pital des enfants malades 149, rue de S~vres 75015 Paris FRANCE **CRI Roussel Uclaf Laboratoires Cassenne 95520 Osny FRANCE RU 41740 (BIOSTIM R) a glycoprotein extract from Klebsiella pneumoniae K201 strain is an imaunomodulating compound currently used in human to prevent infections in chronic bronchitis. We have tested the effects of RU 41740 on the in vitro maturation of human B cells in two systems: (i) the lectin-induced inm~noglobulin (Ig) synthesis, using the pokeweed mitogen (PWM) and (2) the antigen specific antibody response towards mannan, a polysaccharide extract fr~n the cell wall of Candida albicans. In both syst<~s, Ig containing cells were counted after intracytoplasmic anti-isotype in~nunofluorescence staining. Antigenspecific antibody production was measured by radio-autography with tritiated mannan. The addition of either RU 41740 or its lipopolysaccharide fraction n~ned F 1 (RU 41821) has been found inducing a significant increase in generation of ~ - t r i g g e r e d IgM and IgG containing cells and mannan-specific antibody production. These enhancing effects (that r~'ached a maximum at the dose of 0.Olmg/ml) have been foundmore pronounced regarding IgG, both in the non specific and antigen specific syst<~ns. Results obtained with pretreated purified T and B lymphocytes indicate that the activity of either compound is T-cell mediated, thus suggesting that RU 41740 and RU 41821 m~y enhance the production of B cell difft~ren ciating or growth factors by helper T lymphocytes. IMMUNODEPRESSIVE
AGENTS
EFFECT OF CYCLOSPORIN-A ON LYMPHOKINE SECRETION BY HUMAN T CELL CLONES
49
S.Ferrini, A.Nicolin, R.Biassoni, ~A.Moretta Istituto Nazionale per la Ricerca sul Cancro,Genova,Italy;~Ludwig Institute for Cancer Research, Lousanne,Switzerland Since it is well known that human IL-2 producing T cells are heterogeneous with respect to their functional capabilities, we investigated whether differences in sensitivity to CsA existed among different IL-2 producing T cell clones. Clones were derived directly from peripheral blood T cells and screened for their capability to release IL-2 upon PHAinduced stimulation, for eytolytie activity in a lectin-dependent assay and for surface marker expression. Dose response experiments on four different IL-2 producing clones gave similar results, being a concentration of lOOng/ml of CsA highly effective in blocking the PHA or OKT -induced IL-2 production by such clones, doses even higher had virtu3 ally no effect on the IL-2 driven proliferation of the CTL-L mouse cell line used as the indicator system for IL-2 bioassay. Consistently, a selected concentration of lOOng/ ml of CsA was active in blocking IL-2 release by 28 different IL-2 producing T cell clones, independent upon the T4/T 8 surface markers expression. Furthermore, the same doses of CsA were capable of inhibiting~-interferon release by T cell clones. IN VITRO EFFECTS OF RANITIDINE
ON HUMAN LYMPHOCYTE FUNCTIONS.
A. Poggi, S. Sciallero and F. Indiveri. I.S.M.I. - Immunologia Clinica - Universit~ di Genova. The aim of this study is to evaluate the in vitro effects of ranitidine, a histamine 2 receptor antagonist, on human lymphocyte functions. To this end we analyzed the behaviour of peripheral blood lymphocytes (PBL) of 6 healthy donors exposed in vitro to different concentrations of Ranitidine, ranging from I0 mg/ml to i0 ng/ml. Proliferation of PBL upon activation by PHA, PWM and OonA was inhibited up to 80% by the two highest concentrations of the drug. This inhibitory effects was not seen with lower concentrations of the drug, which, on the contrary, enhanced up 63% the responsiveness of PBL to ConA. Ranitidine also inhibited: (a) up to 50% the mitogen induced expression of Class two HLA antigens by T lymphocytes; (b) up to 45% the responsiveness of T cells in autologous mixed lymphocyte reactions of non T-T type. The responsiveness of T cells in allogenic MLR was enhanced in two out the six subjects. These data suggest that Ranitidine may modulate the process of cell to cell cooperation in humans.
50
EFFECT OF RU 41740 ON THE IN VITRO MA~'JRATION OF HUMAN B CRIJS.
48
A.DurandF*, P.Smets**, R.Zalisz** and C.Griscelli*. * Inserm U 132 H6pital des enfants malades 149, rue de S~vres 75015 Paris FRANCE **CRI Roussel Uclaf Laboratoires Cassenne 95520 Osny FRANCE RU 41740 (BIOSTIM R) a glycoprotein extract from Klebsiella pneumoniae K201 strain is an imaunomodulating compound currently used in human to prevent infections in chronic bronchitis. We have tested the effects of RU 41740 on the in vitro maturation of human B cells in two systems: (i) the lectin-induced inm~noglobulin (Ig) synthesis, using the pokeweed mitogen (PWM) and (2) the antigen specific antibody response towards mannan, a polysaccharide extract fr~n the cell wall of Candida albicans. In both syst<~s, Ig containing cells were counted after intracytoplasmic anti-isotype in~nunofluorescence staining. Antigenspecific antibody production was measured by radio-autography with tritiated mannan. The addition of either RU 41740 or its lipopolysaccharide fraction n~ned F 1 (RU 41821) has been found inducing a significant increase in generation of ~ - t r i g g e r e d IgM and IgG containing cells and mannan-specific antibody production. These enhancing effects (that r~'ached a maximum at the dose of 0.Olmg/ml) have been foundmore pronounced regarding IgG, both in the non specific and antigen specific syst<~ns. Results obtained with pretreated purified T and B lymphocytes indicate that the activity of either compound is T-cell mediated, thus suggesting that RU 41740 and RU 41821 m~y enhance the production of B cell difft~ren ciating or growth factors by helper T lymphocytes. IMMUNODEPRESSIVE
AGENTS
EFFECT OF CYCLOSPORIN-A ON LYMPHOKINE SECRETION BY HUMAN T CELL CLONES
49
S.Ferrini, A.Nicolin, R.Biassoni, ~A.Moretta Istituto Nazionale per la Ricerca sul Cancro,Genova,Italy;~Ludwig Institute for Cancer Research, Lousanne,Switzerland Since it is well known that human IL-2 producing T cells are heterogeneous with respect to their functional capabilities, we investigated whether differences in sensitivity to CsA existed among different IL-2 producing T cell clones. Clones were derived directly from peripheral blood T cells and screened for their capability to release IL-2 upon PHAinduced stimulation, for eytolytie activity in a lectin-dependent assay and for surface marker expression. Dose response experiments on four different IL-2 producing clones gave similar results, being a concentration of lOOng/ml of CsA highly effective in blocking the PHA or OKT -induced IL-2 production by such clones, doses even higher had virtu3 ally no effect on the IL-2 driven proliferation of the CTL-L mouse cell line used as the indicator system for IL-2 bioassay. Consistently, a selected concentration of lOOng/ ml of CsA was active in blocking IL-2 release by 28 different IL-2 producing T cell clones, independent upon the T4/T 8 surface markers expression. Furthermore, the same doses of CsA were capable of inhibiting~-interferon release by T cell clones. IN VITRO EFFECTS OF RANITIDINE
ON HUMAN LYMPHOCYTE FUNCTIONS.
A. Poggi, S. Sciallero and F. Indiveri. I.S.M.I. - Immunologia Clinica - Universit~ di Genova. The aim of this study is to evaluate the in vitro effects of ranitidine, a histamine 2 receptor antagonist, on human lymphocyte functions. To this end we analyzed the behaviour of peripheral blood lymphocytes (PBL) of 6 healthy donors exposed in vitro to different concentrations of Ranitidine, ranging from I0 mg/ml to i0 ng/ml. Proliferation of PBL upon activation by PHA, PWM and OonA was inhibited up to 80% by the two highest concentrations of the drug. This inhibitory effects was not seen with lower concentrations of the drug, which, on the contrary, enhanced up 63% the responsiveness of PBL to ConA. Ranitidine also inhibited: (a) up to 50% the mitogen induced expression of Class two HLA antigens by T lymphocytes; (b) up to 45% the responsiveness of T cells in autologous mixed lymphocyte reactions of non T-T type. The responsiveness of T cells in allogenic MLR was enhanced in two out the six subjects. These data suggest that Ranitidine may modulate the process of cell to cell cooperation in humans.
50