Human polyspecific immunoglobulin for therapeutic use induces p21/WAF-1 and Bcl-2, which may be responsible for G1 arrest and long-term survival

High-dose intravenous immunoglobulin (IVIg) is used as therapy in an increa sing number of immune mediated disorders including infections and autoimmun e conditions. IVIg exerts profound effects both in vivo as well as in vitro on humoral and cell-mediated immunity. In this study we investigated wheth er IVIg could alter the pattern of apoptosis and apoptosis related proteins including Bcl-2, Bax, p53, CD95, and p21/ WAF-1, a protein well known to a rrest cells in G1 phase of the cell cycle and finally proliferation marker Ki-67 on peripheral blood mononuclear cells (PBMC). The cells were cultured either unstimulated or with mitogen in the presence or absence of differen t IVIg preparations. A dual effect by IVIg was found. The incidence of apop tosis was elevated in activated Ki-67 and CD95 positive PBMC, whereas it wa s lower in small, nonactivated cells. The cells that survived were associat ed with a striking increase in the expression of p21/WAF-1 suggesting G1 ar rest, A concomitant upregulation of Bcl-2 was also obtained by IVIg exposit ion resulting in long-term survival. We suggest that these abilities of IVI g to alter cell cycle progression and apoptosis could explain some of the b eneficial effects obtained in vivo with IVIg therapy. (C) American Society for Histocompatibility and Immunogenetics, 2001. Published by Elsevier Scie nce Inc.