Biologically active anti-nerve growth factor antibodies in commercial intravenous gammaglobulin

Neurotrophins are regulators of development, survival and function of neuronal and non-neuronal cells, one of the most important of which is nerve growth factor (NGF). Previous studies have demonstrated the presence of antibodies to NGF in normal human serum. It would therefore be predicted that antibodies to NGF would also be present in commercial intravenous gammaglobulin (IVIg). It has been shown in the present investigation that ELISA can detect anti-NGF antibodies in IVIg. The functional activity of these antibodies has been demonstrated after affinity purification, by their inhibitory effects upon (a) the proliferation of the NGF-responsive rat pheochromocytoma cell line PC-12, (b) the differentiation of PC-12 cells as determined by neurite outgrowth. All batches of commercially tested IVIg contained anti-NGF antibodies. Since NGF has an important role in the inflammatory immune response and in cell growth and differentiation, these findings may (a) facilitate our understanding of the mechanisms of action of IVIg, (b) indicate new disease states in which IVIg or its derivatives may exert beneficial effects.