Brief CommunicationInactivated pepsin inhibits neutrophil activation by Fcgamma-receptor-dependent and independent stimuli

- Pepsin is often used for limited proteolysis of immunoglobulins.
- This includes intravenous immunoglobulin (IVIg).
- Here we report a potent immunomodulatory effect of irreversibly inactivated pepsin on neutrophils.
- However, pepsin-treated IVIg products contain insufficient pepsin to bring about these effects.

Pepsin is widely used to produce F(ab′)2 fragments of immunoglobulin G (IgG). In many cases, at least part of the pepsin will remain present in the F(ab′)2 preparation, albeit in (irreversibly) inactivated form. Here we report on a potent immunomodulatory effect of irreversibly inactivated pepsin on activated human neutrophils. Degranulation, induced by coated IgG or via cytochalasin B/N-formyl-Met-Leu-Phe, was measured by quantifying elastase release, and was found to be inhibited in a dose-dependent manner by inactivated pepsin. Since a number of intravenous immunoglobulin (IVIg) products are also treated by limited digestion with pepsin, we investigated if pepsin would be present in quantities large enough to inhibit neutrophil activation. The amounts of pepsin detected in three different pepsin-treated IVIg products were found to be too low to induce an effect, at least in an in vitro setting.