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Abstract

485 CREB = cAMP responsive element binding protein; IL = interleukin; LPS = lipopolysaccharide; MAO = monamine oxidase; NF-κB = nuclear factor-κB; NO = nitric oxide; PBMC = peripheral blood mononuclear cell; PKA = protein kinase A; ROS = reactive oxygen species; SNS = sympathetic nervous system; TNF = tumour necrosis factor. Available online http://ccforum.com/content/8/6/485 IntroductionThe challenge to the immune system that occurs in endotoxaemia involves stimulation of immune cells to produce large amounts of inflammatory cytokines (e.g. IL-1, IL-6 and tumour necrosis factor [TNF]-α). These mediators stimulate both the hypothalamic-pituitary-adrenal axis and the systemic-adrenomedullary sympathetic nervous system (SNS). Consequently, catecholamines are released from preganglionic efferent and postganglionic SNS fibres, innervating a wide range of target organs and thereby regulating endotoxin-induced alterations in vascular resistance and tone, tissue perfusion, cardiac and renal function, and hormone release. Although dopamine is also released, noradrenaline (norepinephrine) and adrenaline (epinephrine) appear to be the principal neurotransmitters in this respect. In early and late stages of severe inflammation, catecholamine production is significantly increased [1]. Nevertheless, it must be noted that circulating catecholamines are poor markers of SNS activation during acute stress, such as occurs in sepsis [2]. Review Clinical review: Immunomodulatory effects of dopamine in general inflammation AbstractLarge quantitaties of inflammatory mediators are released during the course of endotoxaemia. These mediators in turn can stimulate the sympathetic nervous system (SNS) to release catecholamines, which ultimately regulate inflammation-associated impairment in tissue perfusion, myocardial impairment and vasodilatation. Treatment of sepsis is based on surgical and/or antibiotic therapy, appropriate fluid management and application of vasoactive catecholamines. With respect to the latter, discussions on the vasopressor of choice are ongoing. Over the past decade dopamine has been considered the 'first line' vasopressor and is frequently used to improve organ perfusion and blood pressure. However, a growing body of evidence indicates that dopamine has deleterious side effects; therefore, its clinical relevance seems to be more and more questionable. Nevertheless, it has not been convincingly demonstrated that other catecholamines are superior to dopamine in this respect. Apart from its haemodynamic action, dopamine can modulate immune responses by influencing the cytokine network. This leads to inhibition of expression of adhesion molecules, inhibition of cytokine and chemokine production, inhibition of neutrophil chemotaxis and disturbed Tcell proliferation. In the present review we summarize our knowledge of the immunomodulatory effects of dopamine, with an emphasis on the mechanisms by which these effects are mediated.

Duration and Magnitude of Hypotension and Monocyte Deactivation in Patients With Community-Acquired Pneumonia

“…Given the known immunomodulatory effects of vasopressor drugs 25 , and the conflation of physiology and therapy in the SOFA cardiovascular subscale (Table E1), we performed a sensitivity analysis excluding patients who received vasopressors (n=19/525). This demonstrated a persistent association between CV SOFA TOT and day 3 mHLA-DR (p = 0.005) (Table 2, Model 4) in patients who did not receive any vasopressors.…”

“…An additional limitation is that for ethical reasons we cannot extricate the effect of hypotension on immune function from the impact of vasopressor use, a class of drugs which have complex immunomodulatory effects 25 . However, a sensitivity analysis using our multivariate model of CV SOFA TOT vs. day 3 mHLA-DR but excluding patients given vasopressors (n=19/525, Table 2) showed minimal effect on significance testing (p=0.005 in the most parsimonious model).…”

Rho-Kinase Inhibition Reduces Early Microvascular Leukocyte Accumulation in the Rat Kidney following Ischemia-Reperfusion Injury: Roles of Nitric Oxide and Blood Flow

“…Alternatively, it cannot be completely excluded that Y27632 is not entirely specific for Rho kinase. Conversely, dopamine-1 receptor-dependent pro-inflammatory mechanisms overriding NO may explain in part the increased leukocyte accumulation upon exposure to fenoldopam, even in the absence of IR [26]. …”

Catecholamines: Physiological Immunomodulators During Health and Illness

“…Hemorrhage induced a massive increase of circulating epinephrine and norepinephrine concentrations and this increase was paralleled by an elevated number of circulating NK-cells, an increased splenocyte apoptosis rate, and a cytotoxicity of human CD4+ and CD8+ lymphocytes in vivo and in vitro and that this effect was mediated via dopaminergic receptors [121][122][123][124]. Dopamine is active at α-and β-adrenergic receptors but in addition, dopamine exerts its effects via specific dopaminergic receptors that can be found on a large number of cells including lymphocytes [125].…”