Altered levels of soluble CD18 may associate immune mechanisms with outcome in sepsis

Summary The pathogenesis of sepsis involves a dual inflammatory response, with a hyperinflammatory phase followed by, or in combination with, a hypoinflammatory phase. The adhesion molecules lymphocyte function‐associated antigen (LFA‐1) (CD11a/CD18) and macrophage‐1 (Mac‐1) (CD11b/CD18) support leucocyte adhesion to intercellular adhesion molecules and phagocytosis through complement opsonization, both processes relevant to the immune response during sepsis. Here, we investigate the role of soluble (s)CD18 in sepsis with emphasis on sCD18 as a mechanistic biomarker of immune reactions and outcome of sepsis. sCD18 levels were measured in 15 septic and 15 critically ill non‐septic patients. Fifteen healthy volunteers served as controls. CD18 shedding from human mononuclear cells was increased in vitro by several proinflammatory mediators relevant in sepsis. sCD18 inhibited cell adhesion to the complement fragment iC3b, which is a ligand for CD11b/CD18, also known as Mac‐1 or complement receptor 3. Serum sCD18 levels in sepsis non‐survivors displayed two distinct peaks permitting a partitioning into two groups, namely sCD18 ‘high’ and sCD18 ‘low’, with median levels of sCD18 at 2158 mU/ml [interquartile range (IQR) 2093–2811 mU/ml] and 488 mU/ml (IQR 360–617 mU/ml), respectively, at the day of intensive care unit admission. Serum sCD18 levels partitioned sepsis non‐survivors into one group of ‘high’ sCD18 and low CRP and another group with ‘low’ sCD18 and high C‐reactive protein. Together with the mechanistic data generated in vitro, we suggest the partitioning in sCD18 to reflect a compensatory anti‐inflammatory response syndrome and hyperinflammation, respectively, manifested as part of sepsis. The CD18 integrin adhesion molecules support leukocyte adhesion to intercellular adhesion molecules and phagocytosis through complement opsonisation, both processes immediately relevant to the immune response during sepsis. Here, we investigate the role of soluble (s)CD18 in sepsis with emphasis on sCD18 as a mechanistic biomarker of immune reactions and outcome of sepsis.