IL-8 as a circulating cytokine: induction by recombinant tumour necrosis factor-alpha

Abstract

Tumour necrosis factor-alpha (TNF-α) is a pivotal cytokine at the centre of a cascade of cytokines and inflammatory mediators which modulate the host response to infection and trauma, and in particular the metabolic changes resulting in shock and subsequent multi-organ failure. The cytokine IL-8–predominantly an activator and chemotactic factor for circulating polymorphonuclear neutrophil leucocytes–is produced in response to TNF-αin vitro, and high circulating levels of IL-8 are found in septic primates. We have studied the release of IL-8 into the circulation of subjects with chronic hepatitis B undergoing a 10 week pilot trial of recombinant TNF-α (rTNF-α) therapy in doses of 15-100 μg/m², A marked dose-dependent increase in plasma IL-8 levels was seen commencing at 30-60 min after the start of rTNF-α infusion and peaking between 2 and 3 h (mean peak level 4300 ng/l). The temporal pattern of IL-8 production exactly echoed that of IL-6, another component of the cytokine cascade, but peak plasma levels of IL-8 were up to 17 times higher than those of IL-6. This study confirms in vitro data suggesting that IL-8 is a component of the acute circulating cytokine cascade with a potential role in the modulation of the acute immune and metabolic response to infection and trauma.