Reversal of Immunoparalysis in HumansIn Vivo

• DOI: 10.1164/rccm.201204-0645oc
• Publication Date: 2012-07-21T10:35:52Z
• Authors: Jenneke Leentjens; Matthijs Kox; Rebecca M. Koch; Frank Preijers; Leo A. B. Joosten; Johannes G. van d...; Mihai G. Netea; Peter Pickkers
• Keywords: Ex vivo

Reversal of sepsis-induced immunoparalysis may reduce the incidence secondary infections and improve outcome. Although IFN-γ granulocyte-macrophage colony-stimulating factor (GM-CSF) restore immune competence ex vivo stimulated leukocytes patients with sepsis, effects on in are not known.To investigate GM-CSF humans.We performed a double-blind, placebo-controlled, randomized study 18 healthy male volunteers that received Escherichia coli endotoxin (LPS; 2 ng/kg, intravenously) days 1 7 (visits 2). On 2, 4, 6, subjects subcutaneous injections (100 μg/day; n = 6), (4 μg/kg/day; or placebo (NaCl 0.9%; 6).In group, was illustrated by 60% (48-71%) reduction LPS-induced tumor necrosis (TNF)-α plasma concentrations during visit (P 0.03), whereas antiinflammatory IL-10 response significantly attenuated (39% [2-65%]; P 0.15). In contrast, TNF-α were (28% [1-47%]; 0.09), lower (reduction 54% [47-66%]; 0.03). Compared less pronounced group 0.01). Moreover, compared placebo, treatment increased monocyte HLA-DR expression 0.02). The tended same direction as IFN-γ, but statistically significant placebo.IFN-γ partially reverses humans. These results suggest is promising option to reverse immunoparalysis.