AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY 28:38-42 © 1992 MUNKSGAARD
AJJ!!lIt~ Immunologa
Danazol Suppresses Both Spontaneous and Activated Human LymphocyteMediated Cytotoxicity PAOLA VIGAN6, ANNA MARIA DJ BLASIO, MAURO BUSACCA, MARIA GRAZIA SABBADINI, AND MARIO VIGNALI III Department of Obstetrics and Gynecology (P.V., A.MD.B., M.B., M.V.J and V Department ofInternal Medicine (M.G.S.), University of Milano, Milano, Italy ABSTRACT: Danazol is an effective drug in the treatment of endometriosis. Previous reports suggest that it can act by influencing the immune system. Thus, in this study we evaluated whether danazol is able to affect the expression of natural and activated cytotoxicity by human peripheral blood Iymphoctyes (PBL). A cytotoxicity assay by 51Cr release was performed to determine the effect of danazol on lymphocyte cytotoxic response toward an erytroleukemic cell line (K562). A significant suppression ofspontaneous cytotoxicity was observed when lymphocytes were pretreated for 18 h with danazol at the concentration of 5 x 10 -6 M. In addition, danazol could significantly inhibit both IL-2- and INFa-activated cytotoxicity at the concentration of 10 - 5M. Following 18 h exposure to danazol, PBL were able to completely recover their spontaneous but not activated cytotoxic potential upon further in vitro incubation (18 h) in absence of the drug. The biological significance of danazol as an inhibitor of immune function under experimentally defined conditions is discussed in relation to its possible role in vivo. (Am J Reprod Immunol 1992; 28:38-42.) Key words: Danazol, natural killers, interleukin-2, interferon a. INTRODUCTION
There is much experimental evidence that suggests that the development of endometriosis could belinked to abnormalities in both humoral to)
60 50
>
-
30
0 0
U
0~
20 10
0 Basal
IL2
5X6 5 [-Log M] Danazol + IL2
Fig. 2. IL-2-activated, PBL-mediated cytotoxicity toward K562 target cells. Lymphocytes were cultured for 72 h with (.) and without (.) IL-2 in presence (.) and absence of danazol. The bars represent the mean ± SEM cytotoxicity percentage of 5 experiments. "P < 0.001.
DANAZOL AND LYMPHOCYTE-MEDIATED CYTOTOXICITY
60
41
*
50 ~
40
:!::::
o .-
->
AJJ!!lIt~ Immunologa
Danazol Suppresses Both Spontaneous and Activated Human LymphocyteMediated Cytotoxicity PAOLA VIGAN6, ANNA MARIA DJ BLASIO, MAURO BUSACCA, MARIA GRAZIA SABBADINI, AND MARIO VIGNALI III Department of Obstetrics and Gynecology (P.V., A.MD.B., M.B., M.V.J and V Department ofInternal Medicine (M.G.S.), University of Milano, Milano, Italy ABSTRACT: Danazol is an effective drug in the treatment of endometriosis. Previous reports suggest that it can act by influencing the immune system. Thus, in this study we evaluated whether danazol is able to affect the expression of natural and activated cytotoxicity by human peripheral blood Iymphoctyes (PBL). A cytotoxicity assay by 51Cr release was performed to determine the effect of danazol on lymphocyte cytotoxic response toward an erytroleukemic cell line (K562). A significant suppression ofspontaneous cytotoxicity was observed when lymphocytes were pretreated for 18 h with danazol at the concentration of 5 x 10 -6 M. In addition, danazol could significantly inhibit both IL-2- and INFa-activated cytotoxicity at the concentration of 10 - 5M. Following 18 h exposure to danazol, PBL were able to completely recover their spontaneous but not activated cytotoxic potential upon further in vitro incubation (18 h) in absence of the drug. The biological significance of danazol as an inhibitor of immune function under experimentally defined conditions is discussed in relation to its possible role in vivo. (Am J Reprod Immunol 1992; 28:38-42.) Key words: Danazol, natural killers, interleukin-2, interferon a. INTRODUCTION
There is much experimental evidence that suggests that the development of endometriosis could belinked to abnormalities in both humoral to)
60 50
>
-
30
0 0
U
0~
20 10
0 Basal
IL2
5X6 5 [-Log M] Danazol + IL2
Fig. 2. IL-2-activated, PBL-mediated cytotoxicity toward K562 target cells. Lymphocytes were cultured for 72 h with (.) and without (.) IL-2 in presence (.) and absence of danazol. The bars represent the mean ± SEM cytotoxicity percentage of 5 experiments. "P < 0.001.
DANAZOL AND LYMPHOCYTE-MEDIATED CYTOTOXICITY
60
41
*
50 ~
40
:!::::
o .-
->
