Bacterial products and the control of ingestive behavior: Clinical implications

Bacterial products such as lipopolysaccharides (LPS) and muramyl peptides are delivered in the course of infections. They trigger the host's acute phase responses to bacterial infections and are probably involved in the accompanying hypophagia because LPS and muramyl dipeptide (MDP; the minimal immunologically active muramyl peptide) reduce food intake after parenteral administration in animals. LPS and MDP inhibit feeding synergistically through separate but interacting mechanisms. The hypophagic effects of LPS and MDP are presumably mediated by the combined actions of interleukin-l, tumor necrosis factor, and other cytokines. More work is required to understand the interactions between these cytokines, and between bacterial products and cytokines, before cytokine antagonists can be used for treatment of the hypophagia during bacterial infections. As the hypophagia seems to be an early mechanism of host defense, a treatment should be carefully considered. if an intervention is indicated because of a patient's poor condition, inhibitors of eicosanoid synthesis and glucocorticoids may hold more promise for therapy because such substances block LPS and MDP hypophagia. Although LPS can reduce food intake by direct action on the brain, presently available evidence indicates that systemic LPS acts primarily in the periphery to generate a neural signal that is transmitted to the brain and inhibits feeding through the vagus. The exact site where LPS acts on peripheral nerves remains to be identified. LPS hypophagia is conditionable, but conditioning cannot solely account for LPS hypophagia under most test conditions. Whether MDP hypophagia is also conditionable and mediated by vagal afferents is not yet known. Al in all, the putative mediators and mechanisms of LPS and MDP hypophagia suggest some options for a treatment of the hypophagia during bacterial infection, but present knowledge about the mechanisms and interactions of the involved substances is still fragmentary and requires further investigation.