Neural regulation of the proinflammatory cytokine response to acute myocardial infarction

Abstract

Neural regulation of the proinflammatory cytokine response to acute myocardial infarction. Am J Physiol Heart Circ Physiol 287: H791-H797, 2004; 10.1152/ajpheart.00099.2004.-Within minutes of acute myocardial infarction (MI), proinflammatory cytokines increase in the brain, heart, and plasma. We hypothesized that cardiac afferent nerves stimulated by myocardial injury signal the brain to increase central cytokines. Urethane-anesthetized male Sprague-Dawley rats underwent ligation of the left anterior descending coronary artery (LAD) or sham LAD ligation after bilateral cervical vagotomy, sham vagotomy, or application of a 10% phenol solution to the epicardial surface of the myocardium at risk. MI caused a significant increase in tumor necrosis factor (TNF)-␣ and interleukin (IL)-1␤ in the plasma and heart, which was blunted by vagotomy. MI also caused a significant increase in hypothalamic TNF-␣ and IL-1␤, which was not affected by vagotomy. In contrast, epicardial phenol blocked MI-induced increases in hypothalamic TNF-␣ and IL-1␤ without affecting increases in the plasma and heart. These findings demonstrate that the appearance of proinflammatory cytokines in the brain after MI is independent of blood-borne cytokines and suggest that cardiac sympathetic afferent nerves activated by myocardial ischemia signal the brain to increase cytokine production. In addition, an intact vagus nerve is required for the full expression of proinflammatory cytokines in the injured myocardium and in the circulation. We conclude that the sympathetic and parasympathetic innervation of the heart both contribute to the acute proinflammatory response to MI. cardiac sympathetic afferents; cardiac vagal afferents; tumor necrosis factor-␣; interleukin-1␤; hypothalamus

Favorable Neurocognitive Outcome with Low Tidal Volume Ventilation after Cardiac Arrest

“…Peripheral cytokine signaling in turn is transmitted to the brain via vagal afferents, circumventricular organs, and transport of cytokines or downstream molecules across the blood-brain barrier (39)(40)(41)(42)(43). Insults ranging from acute myocardial infarction (44,45) to sepsis (46,47) have been shown to increase intracerebral proinflammatory cytokine levels and associated neuronal injury. Several studies similarly have implicated lung injury as a precipitant of neuroinflammation and brain injury (17)(18)(19)(20).…”

“…Finally, precise causal mechanisms cannot be inferred from this analysis. Several pathways of lung-brain crosstalk have been described in other disease states with biological similarities to PCAS (44)(45)(46)(47). Additional preclinical and clinical investigations are needed to determine their relevance to cardiac arrest and elucidate other mechanisms that may be unique to the constellation of injuries comprised by PCAS.…”

Central Gene Transfer of Interleukin-10 Reduces Hypothalamic Inflammation and Evidence of Heart Failure in Rats After Myocardial Infarction

“…[1][2][3][4][5] Circulating proinflammatory cytokines induce cyclooxygenase-2 (COX-2) activity in the cerebral vasculature, increasing the production of prostaglandins E 2 (PGE 2 ) 6 and indirectly activating the hypothalamic-pituitary-adrenal axis. 7 Recent studies in rats with HF suggest that circulating proinflammatory cytokines also induce the expression of proinflammatory cytokines in cardiovascular regulatory regions of the brain.…”

“…7 Recent studies in rats with HF suggest that circulating proinflammatory cytokines also induce the expression of proinflammatory cytokines in cardiovascular regulatory regions of the brain. 8 -10 Interleukin (IL)-1␤ and tumor necrosis factor (TNF)-␣ appear in the rat hypothalamus early after MI 4,5 and remain present at increased levels in rats with established HF. 4,8 Emerging evidence suggests that proinflammatory cytokines in the brain upregulate the activity of the brain renin-angiotensin system (RAS) 11 and contribute to oxidative stress.…”

Using optogenetics to translate the “inflammatory dialogue” between heart and brain in the context of stress

“…Earlier studies revealed that central infusion of pro-inflammatory cytokines such as IL-1β and TNF-α leads to significant hemodynamic and neurohormonal responses (such as increased arterial blood pressure) that are typical of CVDs, sympathetic activity, and the synthesis of renin, aldosterone and vasopressin [65,66] . Recent studies further showed that myocardial infarction induces the production of cytokines in the hypothalamus, which modulate neurotransmission in the PVN during the subsequent process of heart failure, resulting in elevated sympathoexcitation [67][68][69] . However, chronic central block of TNF-α in a rat model of heart failure returns the concentrations of several neurotransmitters in the PVN to control levels, while retaining the elevation of renal sympathetic nerve activity [70] .…”