Nature medicine
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Neutralization of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1), decreases mortality in several animal models of sepsis. However, recent clinical trials did not show an unequivocal improvement in survival. In contrast to animals, which succumb to shock during the first 72 hours, we found that many patients die much later with signs of opportunistic infections accompanied by downregulation of their monocytic HLA-DR expression and reduced ability to produce lipopolysaccharide (LPS)-induced TNF-alpha in vitro. ⋯ Moreover, IFN-gamma applied to septic patients with low monocytic HLA-DR expression restored the deficient HLA-DR expression and in vitro LPS-induced TNF-alpha secretion. Recovery of monocyte function resulted in clearance of sepsis in eight of nine patients. These data suggest that IFN-gamma treatment in carefully selected septic patients is a novel therapeutic strategy worth pursuing.