Pepsin-immunoregulation hypothesis.

Pepsin exists in macrophages. Phagocytosis of foreign materials increases pepsin activity in macrophages and also causes extracellular release of pepsin from macrophages. Pepsin enhances antibody production by spleen cells against heterologous materials and suppresses that against homologous materials. Pepsin selectively decomposes immune complexes at neutral pH, and intravenous pepsin ameliorates symptoms in autoimmune disease models, such as immune complex glomerulonephritis in MRL/l mice and SLE-like syndromes of NZB/W F1 mice. These results prompted us to propose a "pepsin-immunoregulation hypothesis", according to which pepsin acts as a regulating factor in the immune system.