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n Cardiovascular Journal of South Africa - Sustained white cell cytokine activation in idiopathic dilated cardiomyopathy despite haemodynamic improvement with medical therapy : cardiovascular topic

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Abstract

Cytokine production in idiopathic dilated cardiomyopathy (IDC) may depend on neurohumoral stimulation, haemodynamic impairment or auto-antibody production. We aimed to ascertain the impact of haemodynamic improvements with standard medical therapy and neurohumoral blockade on white cell tumour necrosis factor-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol"&gt;a&lt;/SPAN&gt;&lt;/SPAN&gt; (TNF-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol">a</SPAN></SPAN>) production in patients with IDC. <br>Twenty-seven patients with IDC and NYHA class I to IV heart failure but without evidence of oedema, reduced peripheral perfusion, or elevated plasma endotoxin concentrations were evaluated for indicators of cytokine activation. Plasma TNF-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol"&gt;a&lt;/SPAN&gt;&lt;/SPAN&gt; concentrations were raised (p < 0.001) in patients prior to commencement of medical therapy as compared to controls (n = 27). In addition, endotoxin-free cultured whole blood TNF-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol">a</SPAN></SPAN> production was enhanced (p < 0.02) in the patients. Although plasma TNF-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol"&gt;a&lt;/SPAN&gt;&lt;/SPAN&gt; tended to decrease, excessive whole blood TNF-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol"&gt;a&lt;/SPAN&gt;&lt;/SPAN&gt; production remained unaltered following marked improvements in haemodynamics and functional class (increase in absolute left ventricular ejection fraction = 8.7 &lt;u&gt;+&lt;/u&gt; 2.6%, p < 0.01, 37% in NYHA functional class I after therapy) with six to 12 months of medical therapy (diuretic, angiotensin converting enzyme inhibitor and <SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol">b</SPAN></SPAN>-blocker). Against a role for neurohumoral substances in promoting excessive white cell TNF-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol"&gt;a&lt;/SPAN&gt;&lt;/SPAN&gt; synthesis the angiotensin II receptor antagonist, losartan, failed to modulate white cell TNF-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol"&gt;a&lt;/SPAN&gt;&lt;/SPAN&gt; production in patients with IDC. <br>We concluded that white cell TNF-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol"&gt;a&lt;/SPAN&gt;&lt;/SPAN&gt; overproduction is sustained in patients with IDC despite haemodynamic improvement with standard medical therapy and blockade of angiotensin II receptors. These data suggest that mechanisms other than haemodynamic impairment and neurohumoral activation contribute to excess white cell TNF-<SPAN lang=AF style="FONT-FAMILY: Symbol; mso-ascii-font-family: 'Times New Roman'; mso-hansi-font-family: 'Times New Roman'; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN style="mso-char-type: symbol; mso-symbol-font: Symbol"&gt;a&lt;/SPAN&gt;&lt;/SPAN&gt; production in IDC.

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/content/cardio/16/4/EJC24027
2005-07-01
2016-12-07
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