Arginine availability, arginase, and the immune response

Abstract

Arginine, often found in immunonutrition regimens, is an important modulator of immune system activation. However, the mechanism of how arginine may be beneficial in immunonutrition is poorly understood. This review details the importance of arginine, its metabolism, and ultimately, its physiologic role in critically ill and immunocompromised patients. The metabolism of arginine is determined by the expression of the arginine metabolizing enzymes inducible nitric oxide synthase and two arginase isoforms (arginase I and II). Inducible nitric oxide synthase is induced by T helper I cytokines (interleukin-1, tumor necrosis factor and gamma-interferon), while arginases are induced by T helper II cytokines and other immune regulators such as interleukins 4, 10, and 13, transforming growth factor-beta and prostaglandin E2. Endotoxin induces inducible nitric oxide synthase and arginases I and II. Arginase plays an important role in the production of ornithine, a precursor of proline and polyamines, both of which are necessary for cellular proliferation and wound healing. Arginase also induces nitric oxide synthase activity by competing for arginine availability in the extracellular environment, and producing polyamines, which may modulate macrophage activation. Through limitation of arginine availability in the extracellular environment, arginases also potentially regulate other 'arginine-dependent' immune functions such as T-lymphocyte activation, although this hypothesis remains to be proven. The availability of arginine during critical illness may be regulated by arginase activity. Thus, arginase expression appears to be essential in the regulation of the cellular immune response and the inflammatory process during critical illness.