IL-8 as a circulating cytokine: induction by recombinant tumour necrosis factor-alpha.
Tumour necrosis factor-alpha (TNF-alpha) 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-alpha in 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-alpha (rTNF-alpha) therapy in doses of 15-100 micrograms/m2. A marked dose-dependent increase in plasma IL-8 levels was seen commencing at 30-60 min after the start of rTNF-alpha 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.
Sheron
N
N
Institute of Liver Studies, King's College Hospital School of Medicine and Dentistry, London, UK.
Williams
R
R
D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006509:Hepatitis B / Q000188:drug therapy; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood*; D010865:Pilot Projects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000627:therapeutic use
D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha