Km. Alkarfy et al., Unintended immunomodulation: Part I. Effects of common clinical conditionson cytokine biosynthesis, SHOCK, 13(5), 2000, pp. 333-345
Cytokines are low molecular weight proteins that act in an autocrine, parac
rine and endocrine fashion to regulate and integrate immune effector cell f
unction. Cytokine production is tightly controlled by a complex network of
co-stimulatory and feedback loops. The systemic concentrations of some cyto
kines, most notably tumor necrosis factor and various interleukins, correla
te with the extent of inflammation, and the severity of critical illness an
d patient outcome. Thus, cytokine expression is often monitored and/or mani
pulated as a therapeutic target in studies of sepsis and other inflammatory
conditions. Unfortunately, some therapies designed to modify cytokine resp
onse have failed to improve outcomes in sepsis, and some of these therapies
have actually been harmful. Several common clinical conditions, as well as
, therapeutic interventions significantly influence cytokine expression. Fu
rthermore, the magnitude and extent of these effects may be greater than th
ose produced by immunomodulating therapies. In contrast, other conditions m
ay not produce clinically significant changes in cytokine expression, and m
ust simply be considered when interpreting studies designed to determine th
e effects of immunomodulation. Some conditions may even result in changes i
n the inflammatory response and may thus add to the inflammatory burden of
a critically ill patient. This review provides intensivists and other clini
cians with an overview of the effects of altered physiologic conditions on
cytokine expression. This information is important so that studies measurin
g cytokines can be correctly interpreted and clinical circumstances in whic
h cytokine manipulation is undesirable can perhaps be avoided.