Cytokine signaling during the acute-phase of inflammation, sequential appearance of il-1[beta] and il-6 in myocardial infarct Guillen, Isabel, Marino Blanes, Mar[acute]ia-Jos[acute]e G[acute]omez -Lech[acute]on, and Jos[acute]e V. Castell. Research Center and Department of Internal Medicine, University, Hospital La Fe. Avda de Campanar 21. E-46009 Valencia.
APStracts 2:0056R, 1995.
The purpose of this study was to investigate the significance of the sequential changes in pro-inflammatory cytokines observed in the plasma of patients early after myocardial infarct: a rise in IL -1[beta] (308+/-126 vs. 141+/-78 pg/ml, p<0.01) between 0-2 h, followed by an IL-6 peak (49+/-24 vs. 14.5+/-13 pg/ml, p<0.01) 4-9 h later. No significant changes in TNF-[alpha] were observed at this early stage. The linkage between IL-1[beta] and IL-6 secretions is supported by: a) the ability of patient's plasma drawn early after myocardial infarction, to induce IL-6 mRNA and protein synthesis in cells that may be potential targets in vivo (fibroblasts and endothelial cells); b) suppression of this activity by antibodies against IL-1[beta]; and c) a delay between IL-1[beta] and IL-6 peaks in vivo (4-9 h), which is similar to the time required for maximal IL-6 production in IL-1[beta] stimulated target cells in vitro (6 hours). This sequential signaling might serve as the basis for an amplification mechanism of pro-inflammatory cytokines. In fact, a much greater synthesis of CRP was observed in hepatocytes when stimulated with conditioned media of fibroblasts or endothelial cells, that had been previously incubated with plasma of patients. The results of our work strongly suggest that by inducing IL-6 in potential target cells, IL-1[beta] could act as the primary, but indirect, signal that stimulates acute-phase protein synthesis after myocardial injury. 

Received 10 December 1993; accepted in final form 22 January
1995.
APS Manuscript Number R669-3.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  7 March 1995.