Bromocriptine immunomodulation of experimental SLE and primary antiphospholipid syndrome via induction of nonspecific T suppressor cells.
Bromocriptine (BRC) is a dopamine agonist that suppresses the secretion of prolactin by the pituitary gland and is known to have immunomodulating properties. In the present study, we investigated the effect of BRC on the development of two autoimmune experimental models: (i) systemic lupus erythematosus (SLE), induced by injection of a human anti-dsDNA monoclonal antibody (MIV-7); (ii) primary anti-phospholipid syndrome (PAPS), induced by injection of a mouse anticardiolipin monoclonal antibody (CAM). BRC had a suppressive effect on in vivo autoantibody production, as well as on the appearance of other manifestations of the respective disease. The BRC activity seems to be nonspecific, since the same effect was demonstrated in mice with lupus and with PAPS. These data were supported by the in vitro nonspecific effect of CD8 cells induced in vivo by bromocriptine, on specific lymph node cell proliferation in the presence of the pathogenic monoclonal antibodies (MIV-7 or CAM, respectively), and on the response to an irrelevant autoantigen, myelin basic protein. These data were complemented by the nonspecific suppressive effect by the T-suppressor factor, produced by the CD8 cells, on specific thymidine uptake by lymph node cells from experimental SLE or PAPS in the presence of the immunizing mAb. Injection of CD8 cells from BRC-treated mice with SLE or PAPS abolished the disease development in the lupus and PAPS experimental models. The data suggest a possible novel role of bromocriptine in downregulating autoimmune phenomena through induction of natural nonspecific CD8+ suppressor cells.
Blank
M
M
Department of Medicine B, Sheba Medical Center, Israel.
Krause
I
I
Buskila
D
D
Teitelbaum
D
D
Kopolovic
J
J
Afek
A
A
Goldberg
I
I
Shoenfeld
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000188:drug therapy*; D001323:Autoantibodies / Q000096:biosynthesis / Q000187:drug effects; D001971:Bromocriptine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013491:Suppressor Factors, Immunologic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D013491:Suppressor Factors, Immunologic; D001971:Bromocriptine