Catecholamines: Physiological Immunomodulators During Health and Illness

Abstract

The existence of an immune-endocrine interaction has been reported and the modulatory effects of the natural occurring catecholamines epinephrine, norepinephrine and dopamine as well as of pharmaceutically generated catecholamines like dopexamine on a wide variety of immune functions were demonstrated. Furthermore, it was noticed that these effects are mediated by specific adrenergic and dopaminergic receptors expressed on the surface of immunological target cells. At first, the adrenergic immunomodulation was predominantly investigated in healthy volunteers and profound immunomodulatory effects were reported for endogenously released and exogenously administered catecholamines. To further elucidate the physiological significance of these interactions, investigators tried to reveal the importance of the catecholaminergic modulation of the immune system under pathological conditions like hemorrhagic shock and systemic inflammation, since catecholamines and adrenergic antagonists are frequently used drugs in the treatment of the critically ill. Furthermore, the interaction between catecholamines and the immune system is supposed to be an important factor in the development of autoimmune diseases and may influence their progress. In addition to the effects of peripheral circulating catecholamines, it was demonstrated that catecholamines that are released within the central nervous system may profoundly influence the activity of the peripheral immune system. Starting with a short historical overview over the immunomodulatory effects of blood catecholamines under good health conditions during critical illness and during autoimmune disease will be reviewed and the immunomodulatory effects of centrally released catecholamines will be discussed.

Catecholamines—Crafty Weapons in the Inflammatory Arsenal of Immune/Inflammatory Cells or Opening Pandora’s Box?

“…Thus, there seems to be a universal pattern for catecholamine effects during sepsis, which might be modulated by cellular adrenoceptors: splenocytes are driven into apoptosis, lymphocyte counts decrease (perhaps due to apoptosis), while NK cell numbers increase. Dopamine is another commonly used drug to prevent renal failure and treat moderate hypotension in the critically ill (82). Dopamine also is an agonist of α-and β-adrenergic receptors, but exerts its effects mainly via specific dopaminergic receptors that can be found on a large number of cells including lymphocytes (83).…”

β2-Adrenergic receptor-dependent sexual dimorphism for murine leukocyte migration

“…Stress can affect inflammatory diseases (see Black, 2002(Black, 2002a for review), in part mediated by the effect of stress hormones on leukocyte function (Bierhaus et al, 2006;Bilbo et al, 2002;Dhabhar, 2002;Landmann et al, 1984;O'Leary et al, 1996;Shephard, 2003), and catecholamines mediate interactions between the sympathetic and the immune systems, to alter immune cell activity (Benschop et al, 1997;Downing and Miyan, 2000;Elenkov et al, 2000;Oberbeck, 2006;Straub et al, 1998). Norepinephrine, released from sympathetic nerve terminals, and epinephrine, released from the adrenal medulla (Elenkov et al, 2000), act primarily on α 2 and β 2 adrenergic receptors expressed on most resting and activated immune cells (Barnes, 1995;Barnes, 1999;Kin and Sanders, 2006;Maestroni, 2006;Wahle et al, 2005).…”

Perioperative Haemodynamic Optimisation

“…Likewise, the use of catecholamines such as epinephrine, norepinephrine and dobutamine has been associated with well-recognised complications, such as digital ischaemia and tachyarrhythmias. Additionally, other not so obvious detrimental effects (23) such as stimulation of bacterial growth (24), immunosuppression (25), insulin resistance and increase of oxidation of fatty acids which might play a relevant role in myocardial ischaemia (26) have also been associated with the use of catecholamines. So it seems reasonable to think that manipulating haemodynamics in some patients with pharmacologic agents (fluids and inotropes) to reach predefined goals may expose them to unnecessary risks.…”