Tumor necrosis factor α and leptin: Two players in an animal's metabolic and immunologic responses to infection

ABSTRACT Neurons do not have receptors to detect bacteria or viruses, yet the presence of these microorganisms can cause profound changes in neuronal function and result in the expression of sickness behaviors, including anorexia. Because the immune system has receptors capable of detecting these noncognitive stimuli, to understand why sick animals do not eat well the method by which the immune system transmits a message to the brain has been studied. The focus has been on the cytokines secreted by leukocytes; these include interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNFα). These cytokines are secreted during immune challenge, and numerous studies have shown that both peripheral and central injection of IL-1β, IL-6, and TNFα reduce feed intake. Moreover, these cytokines and their receptors are present in the brain, and inhibiting the secretion of cytokines or blocking their receptors in the brain has been shown to block or abrogate anorexia induced by inflammatory stimuli. These results may be interpreted to suggest that anorexia of infection is mediated by the direct action of cytokines in the brain. However, recent studies indicate that TNFα acts on adipocytes to induce secretion of leptin, the product of the ob gene. Leptin is a blood-borne factor involved in long-term regulation of feed intake and energy expenditure. Thus, another way the immune system may transmit a message to the brain and regulate feed intake is by stimulating leptin production. Surprisingly, the communication between cells of the immune system and adipocytes goes two ways, and leptin is now considered an integral part of the acute phase response and necessary for comprehensive immunocompetence. Thus, the interplay between immune cells and fat cells is yet another example of how seemingly disparate physiological systems are integrated. The effects of TNFα on leptin secretion and the relevance of the interaction between the immune system and adipose tissue are the focus of this brief review.

Implications

Not so long ago, the immune system was thought to operate independently of other physiologic systems. This notion, however, has fallen by the wayside. That tumor necrosis factor α, a classic cytokine of the immune system, interacts with adipocytes and stimulates leptin secretion, and that leptin, a hormone first described for its role in energy balance, interacts with leukocytes and affects the immune response are yet additional examples of how seemingly disparate physiologic systems are integrated. Because domestic food animals are subjected to numerous infectious pathogens (as are all animals) and are genetically selected for high or low feed intake and varying levels of adiposity, understanding how these systems work together in times of good health and in times of disease is critical.

Key Words: Anorexia, Cytokines, Feed Intake, Leptin, Tumor Necrosis Factor

© 2001, by the American Society of Animal Science. All rights reserved.

J. Anim. Sci. 2001. 79:E118-E127