Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition.

Abstract

In addition to activating T and B lymphocytes, interleukin 1 (IL-1) induces several hematologic and metabolic changes typical of host responses to infection and injury. We now report a new biological property, namely, the induction of hypotension. Rabbits given a single intravenous injection of recombinant human IL-I-beta (5 isg/kg) rapidly developed decreased systemic arterial pressure, which reached the lowest levels after 50-60 min and slowly returned to pre-IL-I values after 3 h. Associated with the hypotension, systemic vascular resistance and central venous pressure fell, while cardiac output and heart rate increased. These responses were prevented by ibuprofen given 15 min before the IL-i. A bolus injection of IL-I followed by a 2-h infusion sustained the hypotension and was associated with leukopenia and thrombocytopenia. Ibuprofen given at the mid-point of the infusion reversed the changes in all hemodynamic parameters, but had no effect on the leukopenia or thrombocytopenia. Tumor necrosis factor (TNF) also induced a shock-like state in rabbits. When the dose of IL-1 or TNF was reduced to 1 ,ug/kg, no hemodynamic changes were observed; however, the combination of these low doses of both cytokines resulted in a profound shock-like state including histological evidence of severe pulmonary edema and hemorrhage. Pretreatment with ibuprofen prevented the hemodynamic, leukocyte, and platelet changes induced by the low-dose cytokine combination, and ameliorated the pulmonary tissue damage.These results demonstrate that IL-1, like TNF, possesses the ability to induce hemodynamic and hematological changes typical of septic shock, and that the combination of IL-I and TNF is more potent than either agent alone. These effects seem to require cyclooxygenase products, and suggest that intravenous cyclooxygenase inhibitors may be of therapeutic value in patients with IL-i/TNF-mediated shock.

Significance of clinical variables and selected biochemical markers in predicting the outcome of bovine anaplasmosis

“…It has also been reported that high concentrations of pro-inflammatory cytokines correlate with the prognosis of sepsis and the development of multiple organ dysfunctions (Edith et al 2004). Moreover, the infusion of high concentrations of pro-inflammatory cytokines in rabbits was associated with multiple organ dysfunction syndrome (Kusawa et al 1988). Several studies have suggested that the circulating levels of proinflammatory cytokines could be useful in assessing the severity and in predicting the clinical outcomes of some diseases (Rauchhaus et al 2000;Orro et al 2011;El-Ashker et al 2013;El-Ashker et al 2014).…”

Induction by Toxic-Shock-Syndrome Toxin-1 of a Circulating Tumor Necrosis Factor-Like Substance in Rabbits and of Immunoreactive Tumor Necrosis Factor and Interleukin-1 from Human Mononuclear Cells

“…Animal models for inducing the toxicshock-like state usually use high doses of TSST-1, ranging from microgram to milligram quantities per kilogram of body weight [23], and under these con ditions, circulating IL-1 is clearly being produced [3]. Using anesthetized rabbits our previous studies dem onstrated that low doses of IL-1 induce reversible hypotension and, when given as a constant infusion, a shock-like state [16]. The time course of IL-l-induced hypotension was rapid, and the onset and recovery were nearly identical to those of pyrogenic responses [24].…”

“…Fe male New Zealand white rabbits (weighing ^5 kg) were anesthetized with a single injection of 4 mg of xylazine/kg and 10 mg of ketamine/kg. This com bination of nonbarbituates has been used in previ ous studies in models of septic shock where experi mentally induced changes in hemodynamic parameters were shown to be unaffected by these anesthetics [16]. Catheters were placed in the left carotid artery (PE 50), the pulmonary artery (no.…”

“…Recombinant IL-1 and TNF increase hepatic acute-phase protein synthesis [10], decrease hepatic albumin synthesis [10,11], in duce synovial collagenase and prostaglandin E2 [12], cause release of procoagulant activity from vascu lar endothelium [13], and inhibit lipoprotein lipase synthesis [14,15]. We recently demonstrated that in jection of recombinant human IL-1 (3 or recombinant human TNF decreases systemic arterial pressure in the rabbit and that combined administration of IL-1 and TNF is more potent than either cytokine alone in induction of a shock-like state [16].…”

The cytokine‐mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia

“…One obvious confounding factor is the lack of possible interactions with other mediators, which cannot be taken into account. In in vitro systems this is not a theoretical concern, as it has repeatedly been found that inflammatory mediators may have additive or synergistic effects that markedly differ from their individual biological activities [5].…”