Macrophage Inflammatory Protein-2 Predicts Acute Lung Injury in Endotoxemia

Meena Kalyanaraman, Sabrina M. Heidemann, Ashok P. Sarnaik

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background: Proinflammatory mediators that include tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) and anti-inflammatory mediators such as interleukin-10 (IL-10) modulate the immune response to endotoxemia. IL-10 downregulates the production of TNF-α and MIP-2. Acute lung injury may occur secondary to neutrophil chemotaxis mediated by chemokine MIP-2. We studied the temporal relationship of TNF-α, MIP-2, and IL-10 in rat endotoxemia and correlation of MIP-2 concentrations with acute lung injury. Methods: Ten ventilated rats were randomized to receive an intravenous infusion of 2 mg/kg Escherichia coli lipopolysaccharide (n = 6) or saline placebo (n = 4). Blood pressure was continuously monitored and arterial blood was obtained for lactate, blood gas, TNF-α, IL-10, and MIP-2 measurements at baseline, 2, 4, and 5.5 hours after LPS or saline infusion. Results: Endotoxemia resulted in hypotension, lactic acidemia, and increased alveolar-arterial oxygen gradient (A-a O2 gradient) compared with the placebo group. TNF-α, MIP-2, and IL-10 levels were increased 2 hours after endotoxemia. Subsequently, TNF-α levels declined while IL-10 and MIP-2 levels remained elevated. Control rats had no significant increase in cytokine production at any time point. MIP-2 concentrations correlated with A-a O2 gradient, an indicator of lung injury (r = 0.56, p < 0.001). Conclusions: MIP-2, possibly released by TNF-α stimulation of macrophages, is associated with acute lung injury possibly by inducing neutrophil chemotaxis. IL-10 may exert its counter-inflammatory response by inhibiting the release of TNF-α in endotoxemia.

Original languageEnglish
Pages (from-to)275-278
Number of pages4
JournalJournal of Investigative Medicine
Volume46
Issue number6
StatePublished - Aug 1998

Keywords

  • Acute lung injury
  • Endotoxemia
  • Interleukin-10
  • Macrophage inflammatory protein-α
  • Tumor neurosis factor

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