IMMUNOSUPPRESSIVE ACTIVITY OF 15-DEOXYSPERGUALIN ON NORMAL AND AUTOIMMUNE PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Several experimental conditions were used in this study to evaluate th e in vitro effects of 15-deoxyspergualin on the function of T lymphocy tes, B lymphocytes and monocytes from healthy subjects and patients su ffering from systemic lupus erythematosus. Whilst the secretion of pol yclonal immunoglobulin (Ig) M and IgG from the B lymphocytes of the he althy subjects was diminished by 15-deoxyspergualin, neither the proli ferative 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 inhib it the spontaneous production of polyclonal and anti-DNA IgG antibodie s 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 po ssesses a novel mechanism of pharmacological immunosuppression apparen tly different from that of other immunosuppressants, such as cyclospor in A, FK506 and corticosteroids, that seems to be primarily displayed at the level of autoreactive B cells and monocytes.