Immunoglobulins for Intravenous Use Inhibit TNFα Cytotoxicity In Vitro

Intravenous immunoglobulins (IVIg) have been used as an immunomodulatory therapy in a variety of diseases. Several mechanisms of action have been proposed, one of which is interference with the cytokine network. We have investigated the effect of IVIg on the cytotoxicity of human TNFα. IVIg was capable of protecting L929 fibroblasts from TNFα induced cell death. This effect was not species specific and was mediated by both the Fc and the Fab portion of immunoglobulins. Since the effect was also seen when IVIg was added after the removal of TNFα from the culture medium, it seems to be independent of the interaction of TNFα with its receptor. We conclude that IVIg either act on some point of the TNFα signalling pathway or influence the cell cycle unspecifically. The cytoprotective effect of IVIg potentially could contribute to the beneficial effect described for various diseases.