Chemokines and interleukin-18 are up-regulated in bronchoalveolar lavage fluid but not in serum of septic surgical ICU patients

Our objective was to investigate the levels of chemokines (MIP1-alpha, MCP- 1, and Gro-alpha), Interleukin-18 (IL-18), and Interleukin (IL-6) in bronch oalveolar lavage (BAL) fluid and serum at the onset and ongoing states of s epsis as defined by the American College of Chest Physicians/Society of Cri tical Care Medicine in septic surgical ICU patients. Our summary background data was to understand the significance of compartmentalized inflammatory mediator production in an immunologically active organ (lung) in comparison with levels in the systemic circulation. The study group consisted of 20 s eptic patients and 10 non-septic patients on surgical ICU. At the onset of sepsis, both BAL fluid and serum samples were taken and levels of MIP-1 alp ha, MCP-1, GRO-alpha, IL-18, and IL-6 were measured by ELISA. Furthermore, over a subsequent 8-day period, levels of these mediators were determined i n serum. In some experiments, IL-18 mRNA levels were determined in peripher al blood lymphocytes (PBL) of septic and non-septic patients. At the onset of sepsis, MIP-1 alpha MCP-1, GRO-alpha, IL-18, and IL-6 levels were signif icantly up-regulated in BAL fluid as compared with non-septic controls. In marked contrast, with the exception of IL-18 mRNA and IL-6 peptide, there w as no increase in serum levels of inflammatory mediators determined both at the onset and during the ongoing states of sepsis. Based on the present da ta, monitoring levels of serum chemokines and 1L-18 protein as markers of s epsis might be misleading since despite their non-detection in serum. they were highly up-regulated in the lung tissue compartment. These data might u nderscore the role of MIP-1 alpha, MCP-1, GRO-alpha. and IL-18 in the media tion of local tissue damage. Furthermore, these findings raise the notion t hat mediator measurement in immunologically active organs might serve as pi votal indicators of sepsis prior to the actual fulfillment of specific clin ical criteria that defines the patient as being septic.