Immunoglobulin M-enriched human intravenous immunoglobulins reduce leukocyte-endothelial cell interactions and attenuate microvascular perfusion failure in normotensive endotoxemia

Clinical studies indicate potential differences in the efficacy of immunoglobulin (Ig) preparations in patients with sepsis. A recent meta-analysis showed improved survival rates with IgM-enriched Igs. It was the objective of the present study to characterize microcirculatory actions of different clinically used Ig preparations in a rodent endotoxin model by intravital microscopy. Male Syrian golden hamsters 6 to 8 weeks old with a body weight of 60 to 80 g were investigated by intravital fluorescence microscopy. Endotoxemia was induced by administration of 2 mg/kg (i.v.) endotoxin (LIPS, Escherichia coli). Two different Ig preparations containing IgM, IgA, and IgG (intravenous IgM group; n = 6; 5 mL Pentaglobin/kg body weight, i.v.) or exclusively IgG (intravenous IgG group; n = 5; 5 mL Flebogamma/kg body weight, i.v.) were applied 5 min before LPS. Saline-treated endotoxemic animals served as controls (control; n = 8). In controls, LPS induced massive leukocyte-endothelial cell interactions, pronounced microvascular leakage, a decrease of systemic platelet count, and distinct capillary perfusion failure (P < 0.05). Both intravenous IgM and IgG reduced venular leakage (P < 0.05) and ameliorated the decrease in platelet count (P < 0.05). Of interest, intravenous IgM was capable of significantly (P < 0.05) reducing leukocyte adhesion in venules. This was associated with normalization of capillary perfusion at 24 h of endotoxemia, whereas intravenous IgG could not prevent LPS-mediated microvascular perfusion failure. We demonstrate that IgM-enriched Igs are superior to IgG alone in attenuating LPS-induced leukocytic inflammation and microcirculatory dysfunction. Our findings can explain better efficacy of IgM-enriched Igs in patients with severe sepsis.