Differences in arterial and mixed venous IL-6 levels: The lungs as a source of cytokine storm in sepsis

Background. Several investigators have shown that blood levels of interleukin 6 (IL-6) correlate with the severity of illness in critically ill or injured patients. However, little is known about differential arterial and venous blood levels of the cytokine, especially across the lungs. Methods. We measured differences in IL-6 levels in pulmonary and systemic arterial blood and then documented the production or elimination of IL-6 by the lungs in 19 patients with severe illness. Prospective data were obtained from multiple, simultaneous systemic arterial (ART) and mixed venous (MV) blood samples that were drawn for IL-6 analysis from systemic arterial and pulmonary artery catheters in 7 patients awaiting vascular operation and in 12 trauma patients being treated in the intensive care unit. Results. A lung disorder was present in 5 patients (pneumonia [n = 1], lung trauma [n = 4]) and absent in the remaining 14 patients. The following data were obtained (mean ± SD) from the highest MV IL-6 levels (pg/mL) in each patient. In patients with a lung disorder (n = 5) compared with those with no disorder (n = 14), ART IL-6 was 9309 ± 12, 521 versus 134 ± 128 (P =.010), MV IL-6 was 5516 ± 7420 versus 137 ± 129 (P =.011), the absolute difference was 3793 ± 5271 versus-3 ± 15 (P =.011), and the percentage difference was 37.4% ± 29.8% versus 1.5% ± 12.3% (P =.001). The ART and MV IL-6 levels tended to be much higher in the 5 patients with pneumonia (n = 1) and lung injuries (n = 4) than in the patients without apparent pulmonary problems. In addition, the patients with a primary lung disorder demonstrated a net increase in IL-6 levels across the lungs, whereas there was no increase, but rather, a net reduction of IL-6 levels across the lungs in patients without a lung disorder. Conclusions. The lung appears to be a major producer of IL-6 in patients with an inflammatory lung process. There is a 39% increase in the level of IL-6 as it passes through inflamed lung, producing a marked difference in ART and MV IL-6 levels. Normal lung demonstrated little effect on either ART or MV IL-6 levels.