[Erythropoiesis during antiepileptic treatments in childhood].
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Biomedical subjects
Publications and source records attributed to F Marceau.
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Des-Arg9-bradykinin (BK) is a selective agonist of the B1 type receptors for kinins. The biological responses to des-Arg9-BK are known to be selectively up-regulated following some types of tissue injury. Two models using rabbits were previously characterized. Firstly, in vivo, lipopolysaccharide (LPS) induces a state of sensitivity to des-Arg9-BK, which becomes a hypotensive peptide. Pretreatment of rabbits with dexamethasone sodium phosphate (DEX) did not modify the induction of cardiovascular sensitivity by LPS. Secondly, isolated rabbit aortic strips incubated in vitro exhibit a spontaneous, time-dependent increase in their responsiveness to des-Arg9-BK. This up-regulation process is selectively inhibited by DEX and stimulated by LPS applied in vitro. DEX application prevented the stimulant effect of LPS in vitro. A variety of growth factors and interleukins as well as interferon-gamma, serotonin, bradykinin and the metalloprotease inhibitor 2-mercaptoethanol were ineffective in modulating the spontaneous up-regulation of contractile responses to des-Arg9-BK. Of the known substances which do modulate this system, only epidermal growth factor (EGF) enhanced aortic contractions to des-Arg9-BK following an acute (15 min) exposure near the end of the 6-hour incubation period used in these studies. The possible involvement of des-Arg9-BK and related peptides in immunopathology is discussed.
Solid-phase enzyme immunoassays (with high-turnover acetylcholinesterase as label) for human IL-1 alpha and IL-1 beta were applied to quantify the production of these factors by cultured human umbilical vein endothelial cells (HUVECs). Immunoreactive IL-1s exhibited a typical pattern in HUVECs, under either basal or stimulated conditions: the alpha form was predominant over the beta form and the cell-associated IL-1s measured were more abundant than the material recovered in the supernatants. Bacterial lipopolysaccharide (LPS, 0.5-5 micrograms/ml) significantly increased the basal production of IL-1. Pulses of recombinant IL-1 alpha or -beta or of TNF-alpha followed by a 24 h culture period were also associated with an increased endothelial production of IL-1, with a higher proportion of material secreted in the supernatants as compared with LPS. Other cytokines applied as pulses failed to induce the IL-1s or to modify LPS-induced production of IL-1: they include IL-2, immune interferon, GM-CSF, TGF-beta and EGF. Pharmacological modulators of LPS-induced IL-1 production were identified: glucocorticoids were inhibitors whereas retinoic acid and 1.25-dihydroxy-vitamin D3 had no effects and prostaglandin E2 and IBMX were weak inhibitors. There is no evidence that IL-1 alpha and IL-1 beta are regulated differently in HUVECs, but several significant differences from the monocyte were observed in the regulation of HUVEC IL-1 production.