Lung as source of Macrophage migration inhibitory factor (MIF) in septic shock

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PURPOSE: To assess the lung as a source of Macrophage Migration Inhibitory Factor (MIF) in septic shock patients.

METHODS: Nine adult patients with septic shock in the Medical Intensive Care Unit (MICU) participated in the study. Blood samples were collected pre-lung (pulmonary artery or central venous catheter) and post-lung (arterial line catheter) at 12 hours, 24 hours and then daily from the time of diagnosis. In one patient bronchial alveolar lavage (BAL) was collected on day 4. MIF was measured using ELISA and differences in plasma MIF concentration pre vs. post lung were assessed using paired t-test on signed ranks.

RESULTS: The mean age of patients was 57.6 years (range 25–82). Blood from six patients were culture positive. There was a wide variation in plasma MIF concentrations in both pre-lung (0.2–64.7ng/ml) and post-lung (0.2–76.4ng/ml). However, there was a significant increase in the median MIF level of the post-lung blood (3.9ng/ml) compared to pre-lung blood samples (2.9ng/ml, p=0.005). These findings were independent of the source or nature of the infection. In addition, the BAL had an MIF concentration greater than 80ng/ml, which was over 3 fold higher than in the blood drawn at the same time (pre-lung 16; post-lung 24ng/ml). This indicates a significant positive concentration gradient between the alveolar epithelial lining fluid and the plasma.

CONCLUSION: This study demonstrates for the first time in humans, that the lung is a major source of MIF in septic shock.

CLINICAL IMPLICATIONS: Septic shock induces a hyper-systemic inflammatory reaction, which may have a detrimental effects including profound cardiopulmonary collapse. MIF is a pro-inflammatory mediator that plays a critical role in sepsis, as well as being a known cardiac depressant. Our previous animal studies demonstrate that MIF contributes to cardiac dysfunction in severe sepsis and that its inhibition, in a clinically relevant time frame, can dramatically improve cardiac function and survival. Recognizing the lung as an inflammatory organ and a major source of MIF may offer future therapy targets to improve outcome in septic shock.

DISCLOSURE: Hans Lee, No Financial Disclosure Information; No Product/Research Disclosure Information

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