How can we modulate cytokine production and action?

Abstract

The loss of body weight and development of cachexia are common signs associated with several diseases. Net muscle protein catabolism is the result of a neuronal and endocrinological response, the main hormone involved in this process being cortisol [1]. Besides this, a number of pathological situations (e.g. cancer, infection, trauma, surgery) lead to activation of the immunological system which, in particular, involves the release of mediators. Among these, cytokines play a preeminent role. Cytokines are now classified according to the cell subset synthesizing them (i.e. Th1 and Th2) and their main action (i.e. proversus anti-inflammatory). The main Th1 cytokines are tumor necrosis factor(TNF), interleukin (IL)-1 and and interferon(IFN). The main Th2 cytokines are IL-4 and IL-10. A notable exception to this classification is IL-6, which is synthesized by Th2 cells but is more a proinflammatory cytokine (PIC) [2]. Th1 cytokines inhibit Th2 cytokine production and vice versa. PICs contribute to protein wasting via several mechanisms, including a direct effect on: (i) protein turnover (i.e. net protein catabolism) increasing protein catabolism through NFB activation [3] and activation of the ubiquitinproteasome system [4, 5], especially activation of E3 ligases atrogin-1 and MURF-1 [6–8], decreasing protein synthesis through inhibition of eIF2B [9] or other factors involved in the translation process such as 4E-BP1 [10], and (ii) amino acid metabolism and oxidation through gluconeogenesis [11]. Also, cytokines potentiate cortisol and glucagon action at the target tissue level (i.e. muscle and liver, respectively) and blunt IGF-1 production and action in muscle [6]. However, the problem is complicated by the fact that each individual PIC has a more or less significant effect on specific aspects of protein Lochs H, Thomas DR (eds): Home Care Enteral Feeding. Nestlé Nutrition Workshop Series Clinical & Performance Program, vol 10, pp 219–232, Nestec Ltd., Vevey/S. Karger AG, Basel, © 2005.