Unintended immunomodulation: Part II. Effects of pharmacological agents on cytokine activity

Cytokines are proteins that are produced by immune and non-immune cells, and they function as mediators to facilitate cellular communication. Their production is regulated by a complex network of co-stimulatory and feedback loops that responds to a variety of stimuli. Several pharmacological agents have been found to alter systemic concentrations and/or the activity of different cytokines via a variety of mechanisms, including changes in biosynthesis, secretion, and/or stability. Many of the agents that modulate cytokine levels commonly are used in the management of critically ill patients. Catecholamines for example, have been found to promote the secretion of anti-inflammatory cytokines, and, therefore, may alter acute inflammatory processes such as sepsis. Antimicrobials have multiple effects on cytokine production, either secondary to the release of endotoxins from gram-negative bacteria or via direct activity on cytokine expression at the transcriptional and/or post-transcriptional level. Pentoxifylline has multiple effects on the immune system, but inhibition of pro-inflammatory cytokine release predominates. The reminder of the known drug-cytokine interactions and their effect on the inflammatory process are discussed. Information on the pharmacodynamic effect of drugs is limited, and our understanding of the clinical significance of these observations awaits further investigation. This review was designed to provide intensivists and other clinicians with useful information regarding the effect of medications on cytokine activity. It is also intended to help researchers and clinicians to optimize the design of studies of pharmacotherapeutic modulation of cytokines and to avoid the use of some agents in clinical circumstances in which cytokine manipulation is undesirable.