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Leukocytic Cytokines Regulate Growth Rate and Composition Following Activation of the Immune System¹

Department of Avian Sciences, University of California, Davis 95616

Abstract

When an immune response is triggered by an infectious challenge the pro-inflammatory cytokines interleukin-1 (IL-1), IL-6, and tumor necrosis factor- (TNF) are released. These cytokines mediate a stress response consisting of specific behavioral, cellular, and metabolic changes that alter the partitioning of nutrients away from growth and toward processes that support the immune and inflammatory responses. They act directly on most tissues of the body through specific receptors, and they induce distinct endocrine changes that further impair growth, including increased glucocorticoids and decreased insulin like growth factor-I. Anorexia induced by pro-inflammatory cytokines accounts for 70% of the growth reduction in young chicks, with the remainder due to tissue-specific changes in metabolism. In chick skeletal muscle, IL-1 and TNF act synergistically to increase the rate of protein degradation. In vivo, IL-1 induces the release of corticosterone that decreases the rate of skeletal muscle protein synthesis and further slows skeletal muscle accretion. Conversely, pro-inflammatory cytokines and corticosterone elevate liver protein synthesis due to increased secretion of acute-phase proteins. Thus, an inflammatory response orchestrates a change in both the rate and the composition of growth in a manner that varies directly with the amount of pro-inflammatory cytokines released. Endogenous mediators that block the release or action of pro-inflammatory cytokines ameliorate the growth suppression that accompanies an immune response. These include the IL-1 receptor antagonist and solubilized receptors. The ratio of dietary (n-3) to (n-6) fatty acid also modulates the growth depression induced by an inflammatory response. An unanswered question is the degree to which specific (adaptive) immune responses impair growth. The profiles of cytokines released allow speculation that inflamma- tory and T_H1 responses are most growth suppressive and T_H2 responses are more benign.

Key Words: Cytokines • Growth • Immunomodulation • Appetite • Muscle

¹ Supported in part by Grant CRCR-1-1885 from the USDA Agriculture Competitive Research Grant Program.

² To whom correspondence should be addressed.