Dynamic Expression of IL-6 Trans-Signalling Molecules in the Lungs of Preterm Baboons Undergoing Mechanical Ventilation

Abstract

Background: Interleukin (IL)-6, when complexed with soluble IL-6 receptor (sIL-6R), has emerged as an important modulator of chemokine expression and leukocyte recruitment during inflammation and in this state can be specifically antagonised by soluble gp130 (sgp130). The expression of these modifiers of IL-6 activity during ventilator-induced inflammation remains poorly understood. Objectives: To ascertain the expression pattern of IL-6, sIL-6R and sgp130 in response to mechanical ventilation in the preterm neonatal lung and define its relationship to associated markers of inflammation. Methods: Inflammatory cell recruitment and expression of IL-6, sIL-6R, sgp130, IL-8 and monocyte chemotactic protein-1 (MCP-1) were quantified in tracheal aspirate fluid collected over a 14-day period from preterm (125 days) baboons undergoing mechanical ventilation. Results: Over the period of ventilation, the ratio of agonistic IL-6/sIL-6R increased 4.3-fold between days 3 and 10–11 (p < 0.01) while the ratio of antagonistic sgp130/IL-6 decreased 2.6-fold over the same period (p < 0.05). Over the same period, the relative numbers of neutrophils compared to mononuclear cells shifted from an excess of 1.8 on day 1 to 0.6 on day 14 (p < 0.01). Both IL-8 and MCP-1 were elevated between days 1 and 10–11 of ventilation (p < 0.01). Conclusions: In the ventilated preterm baboon lung, expression of sIL-6R and dynamic modulation of sgp130 expression appear to modulate the activity and inflammatory potential of IL-6.