Production of systemic and hypothalamic cytokines during the early phase of endotoxin fever.

Changes in concentrations of cytokines in plasma and in hypothalamic push-pull perfusates of guinea pigs were measured within the 1st hour after intramuscular injections of bacterial lipopolysaccharide (LPS; Escherichia coli, 20 micrograms/kg) or solvent (0.9% saline). In control animals injected with solvent, interleukin (IL)-1 and tumor necrosis factor alpha (TNF-alpha) were not detectable in plasma. Only IL-6 was present in picogram quantities. Within 45 min after injection of LPS, the concentrations of IL-1, TNF-alpha, and IL-6 increased in the plasma: by several orders of magnitude for TNF-alpha and about tenfold for IL-G. Picogram amounts of biologically active IL-1 were detected in plasma after injection of LPS. No steady state levels of systemic cytokines were reached during the experimental period. In hypothalamic perfusates of animals injected with the solvent, no IL-1 was detectable. TNF-alpha could be detected at higher concentrations than IL-6. IL-6 was detectable at tenfold lower concentrations than in the plasma. In animals injected with LPS, the hypothalamic concentration of IL-6 started to increase during the period 15-30 min and the concentrations of TNF-alpha during the period 30-45 min after LPS injection. The concentrations of IL-6 increased by 300-400% and did not exceed picogram values. No progressive increase of hypothalamic levels of these cytokines was observed during the time course of the experiment. The method used did not detect any changes in the amount of biologically active IL-1 in hypothalamic perfusates of LPS-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)