The complex interplay between neural and endocrine responses following food intake regulates ingestive behaviour and ultimately determines subsequent energy intake. These processes include cognitive, gastrointestinal-derived and metabolic mechanisms. Such physiological responses to the ingestion of food initiate short- to medium-term inhibition of intake (satiety). However, in clinical states in which systemic inflammation is evident there is a more profound satiety response and a clear absence of motivation to eat that is evident as loss of appetite. These negative influences on energy intake can contribute to poor nutritional status, and consequently poor physical function, and impact on rehabilitation and recovery. Cytokine mediators of the inflammatory response directly influence feeding behaviour at the hypothalamic nuclei and may explain the lack of motivation and desire for food. However, additional detrimental effects on appetite are brought about because of alterations in intermediary metabolism present in inflammation-induced catabolism. This process forms part of the host response to inflammation and may explain symptoms, such as early satiety, frequently reported in many patient groups. In clinical states, and cancer in particular, pharmacological strategies have been employed to ameliorate the inflammatory response in an attempt to improve energy intake. Some success of this approach has been reported following administration of substrates such as EPA. Novel strategies to improve intake through administration of anti-cytokine drugs such as thalidomide may also be of benefit. However, drugs that oppose the actions of neurotransmitter pathways involved in central induction of satiety, such as 5-hydroxytryptamine, have failed to improve intake but appear to enhance enjoyment of food. Such findings indicate that therapeutic nutritional targets can only be achieved where novel pharmacological therapies can be supported by more innovative and integrated dietary management strategies. Many of these strategies remain to be elucidated.
