PubMed · 7928173
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U Janssens, P Hanrath. 1994. [Shock].. https://pubmed.ncbi.nlm.nih.gov/7928173/
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Effects of soluble recombinant human type I interleukin-1 receptor (sIL-1RI) were evaluated in 18 volunteers given intravenous endotoxin and randomized to placebo (n = 6), low-dose (n = 6), or high-dose (n = 6) sIL-1RI. Soluble IL-1RI decreased IL-1 beta (P = .001), but decreased IL-1ra (P = .0001), and resulted in 10-fold and 43-fold dose-related increases in sIL-1RI-IL-1ra complexes compared with placebo (P < or = .001). High-dose sIL-1RI was associated with increased levels of immunoactive tumor necrosis factor-alpha (P = .02), IL-8 (P = .0001), and cell-associated IL-1 beta (P = .047). C-reactive protein levels were higher after sIL-1RI than placebo (P = .035). Soluble IL-1RI decreased the severity of chills (P = .03), but did not alter other symptoms, changes in temperature, systemic hemodynamic responses, or changes in leukocyte and platelet number. Thus, sIL-1RI had no discernable antiinflammatory effect following endotoxin administration due in part to low levels of circulating IL-1 beta and neutralization of IL-1ra inhibitory function. This latter interaction represents an indirect mechanism of agonist activity elicited by sIL-1RI and may contribute to increases in inflammatory mediators, limiting therapy with sIL-1RI during endotoxemia.
Interleukin-1 (IL-1) is a proinflammatory cytokine that participates in the activation of the acute-phase plasma protein genes in hepatic cells during infection and injury. In human hepatoma HepG2 and Hep3B cells, IL-1 beta induced production of the granulocyte colony-stimulating factor (G-CSF) in a dose-dependent manner. Activation of G-CSF gene expression was an early and transient response. In HepG2 cells, G-CSF mRNA was strongly upregulated 2 hours after IL-1 beta treatment and returned to the pretreatment level by 6 hours. The secreted G-CSF was biologically active, as shown by the induction of gene transcription through the G-CSF receptor. Maximal G-CSF activity released to culture medium occurred after 8 hours. Previous studies have shown that liver expression of G-CSF was augmented in mice challenged by inflammatory stimuli. Our data suggest that IL-1 beta mediates, at least in part, this cytokine activation program in parenchymal cells and that liver-derived G-CSF may contribute to the regulation of hematopoiesis during the acute-phase response.
Cytokines are a large and rapidly expanding group of polypeptides produced by many different cell types. Increasing interest has been focused on the role of cytokines as mediators of metabolic, immunological and endocrine responses to surgery. The cytokine response in patients undergoing cardiac surgery during cardiopulmonary bypass (CPB) is fairly well-defined and dominated by the proinflammatory cytokines IL-6, TNF alpha and IL-8 and the antiinflammatory cytokine IL-10. Little is known about the cytokine response in patients who develop postoperative complications but CPB with mechanical trauma and blood contact to artificial membranes is definitely an unphysiological state and may contribute to an uncontrollable response similar to that of patients with multiorgan failure and septic shock.