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Abstract

The anti-inflammatory cytokine IL-10 is up-regulated in response to TNF-alpha suggesting a control mechanism of inflammation. In addition, we recently found systemic IL-10 release in response to acute stress reactions in the absence of any systemic inflammation. In vitro and in vivo studies in experimental models suggest that catecholamines induce IL-10 release via a cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) dependent pathway. Here we studied patients for plasma IL-10 after acute myocardial infarction, a very stressful event without significant signs of systemic inflammation. In fact, the activation of the sympathetic system initiated by cardiac infarction was accompanied by a temporary systemic release of IL-10. Catecholamine induced IL-10 may be released by different cells. Recently, we demonstrated that catecholamines directly stimulate the IL-10 promoter/enhancer via a cAMP/PKA pathway in monocytic cells. A cAMP responsive element (CRE) was identified as major target. Here we show that there is no influence of catecholamines on the IL-10 promoter activity in T-cells. In contrast to monocytic cells, in T-cells cAMP-induced PKA-dependent phosphorylation of the CRE-binding protein 1 (CREB-1) seems to play a marginal role in IL-10 induction, which was reflected by a low cAMP-dependent IL-10-promoter/enhancer stimulation in reporter gene assays. Thus, catecholamines are directly involved in the regulation of IL-10 expression in monocytic but not in T-cells after acute stressful conditions.

Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance

“…Atherosclerosis represents one of the key factors of cardiovascular and cerebrovascular diseases: the inflammation-related predominant Th1 response has also been implicated in the pathophysiology of chronic heart failure [137, 138] and heart failure after acute myocardial infarction [139]. The stress-related Th2 predominant response seems to be associated with acute coronary syndromes: acute exogenous or endogenous stress factors can trigger unstable angina, sudden cardiac death and acute myocardial infarction [140, 141], condition in which was found, in relation to sympathetic system activation and catecholamines release, an increase of IL-6 [142, 143] and IL-10 [144, 145]. Th2 polarized response also promotes fibrosis in general, and cardiac fibrosis in particular [146].…”

Some Aspects of the Normal Role of Neuromodulators in the Immune System

“…Norepinephrine inhibits energy metabolism (oxygen consumption) of human peripheral blood mononuclear cells via adrenergic receptors [18]. Catecholamines induce interleukin-10 (IL-10) release in patients suffering from acute myocardial infarction by transactivating its promoter (cAMP, PKA dependent) in monocytes, but not in T-cells ( [19]. Beta-adrenergic agonists induce a shift in the human type-1/type-2 cytokine balance toward a type-2 response [20].…”