Proinflammatory cytokines, nutritional support, and the cachexia syndrome: interactions and therapeutic options

Abstract

Background: Protein calorie malnutrition remains endemic in hospitalized patients with both acute and chronic inflammation secondary to either cancer, chronic infectious processes, surgical injury, trauma, or burns. For the patients who cannot support themselves by enteral feeding, total parenteral nutrition remains an essential tool to minimize nitrogen losses and replete the depleted patient. However, in patients with active inflammation, nitrogen retention and lean tissue accretion are often impaired during total parenteral nutrition. Production of humoral factors, including proinflammatory cytokines, regulates many of the anabolic and catabolic processes that accompany inflammation.

Methods: The investigators' experience with total parenteral nutrition and proinflammatory cytokines is reviewed.

Results: Cytokines such as interleukin-1, tumor necrosis factor-alpha, and, in particular, interleukin-6 appear to play central roles in both the loss of skeletal muscle protein and the initiation of the acute phase response to inflammation, as well as in modulating the utilization of exogenously administered nutrients.

Conclusions: Although innovative second- and third-generation nutritional formulations for the acutely ill patient may represent one approach for improving the effectiveness of total parenteral nutrition, understanding the humoral response to inflammation and modifying cytokine actions pharmacologically may prove equally effective in improving the utility of exogenously administered nutrients. Future studies need to determine whether the effectiveness of exogenously administered nutrients in the patient with inflammation can be improved by efforts to modulate the proinflammatory cytokine response through cytokine inhibitors or antagonists.