Immunosuppressive activity of 15-deoxyspergualin on normal and autoimmune peripheral blood mononuclear cells.
Several experimental conditions were used in this study to evaluate the in vitro effects of 15-deoxyspergualin on the function of T lymphocytes, B lymphocytes and monocytes from healthy subjects and patients suffering from systemic lupus erythematosus. Whilst the secretion of polyclonal immunoglobulin (Ig) M and IgG from the B lymphocytes of the healthy subjects was diminished by 15-deoxyspergualin, neither the proliferative response of normal T and B cells to mitogenic stimulation nor the cytokine secretory capacity of these cells (e.g. interleukin-2, -4, -6 and gamma-interferon) and monocytes (e.g. interleukin-1 beta and -6) were affected by the drug. In contrast, on the mononuclear cells obtained from the lupus patients not only did 15-deoxyspergualin inhibit the spontaneous production of polyclonal and anti-DNA IgG antibodies but also suppressed interleukin-1 beta secretion from the monocytes. Other functional responses of T and B cells and monocytes from lupus patients, including mitogenic activation and cytokine secretion, were not altered by the drug. These data suggest that 15-deoxyspergualin possesses a novel mechanism of pharmacological immunosuppression apparently different from that of other immunosuppressants, such as cyclosporin A, FK506 and corticosteroids, that seems to be primarily displayed at the level of autoreactive B cells and monocytes.
Nicoletti
F
F
Institute of Internal Medicine, Infectious Diseases and Immunopathology, University of Milan, Italy.
Borghi
M O
MO
Barcellini
W
W
Fain
C
C
Beltrami
B
B
Del Papa
N
N
Schorlemmer
H U
HU
Mottola
L
L
Meroni
P L
PL
D016207:Cytokines / Q000097:blood*; D004247:DNA / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology; D008214:Lymphocytes / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects*
D016207:Cytokines; D006146:Guanidines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D004247:DNA; C037258:gusperimus