Unintended immunomodulation: Part II. Effects of pharmacological agents oncytokine activity

Cytokines are proteins that are produced by immune and non-immune cells, an d they function as mediators to facilitate cellular communication. Their pr oduction is regulated by a complex network of co-stimulatory and feedback l oops that responds to a variety of stimuli. Several pharmacological agents have been found to alter systemic concentrations and/or the activity of dif ferent cytokines via a variety of mechanisms, including changes in biosynth esis, secretion, and/or stability. Many of the agents that modulate cytokin e levels commonly are used in the management of critically ill patients. Ca techolamines for example, have been found to promote the secretion of anti- inflammatory cytokines, and, therefore, may alter acute inflammatory proces ses such as sepsis. Antimicrobials have multiple effects on cytokine produc tion, either secondary to the release of endotoxins from gram-negative bact eria or via direct activity on cytokine expression at the transcriptional a nd/or post-transcriptional level. Pentoxifylline has multiple effects on th e immune system, but inhibition of pro-inflammatory cytokine release predom inates. The reminder of the known drug-cytokine interactions and their effe ct on the inflammatory process are discussed. Information on the pharmacody namic effect of drugs is limited, and our understanding of the clinical sig nificance of these observations awaits further investigation. This review w as designed to provide intensivists and other clinicians with useful inform ation regarding the effect of medications on cytokine activity. It is also intended to help researchers and clinicians to optimize the design of studi es of pharmacotherapeutic modulation of cytokines and to avoid the use of s ome agents in clinical circumstances in which cytokine manipulation is unde sirable.