DEFECTIVE TOLERANCE TO THE TOXIC AND METABOLIC EFFECTS OF INTERLEUKIN-1

被引:27
作者
MENGOZZI, M [1 ]
GHEZZI, P [1 ]
机构
[1] MARIO NEGRI INST PHARMACOL RES,IMMUNOL LAB,VIA ERITREA 62,I-20157 MILAN,ITALY
关键词
D O I
10.1210/endo-128-3-1668
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effect on food intake, body weight, and survival of mice given recombinant lipopolysaccharide (LPS), tumor necrosis factor/cachectin (TNF), or interleukin 1 (IL-1) (5-mu-g/mouse, ip, twice daily) was studied. All agents induced a rapid reduction of food intake and body weight after 1 day of treatment. Unlike TNF and LPS, IL-1 given as two daily administrations of 5-mu-g was lethal within 3 days. Mice treated with LPS or TNF rapidly developed tolerance to their anorectic effect, whereas tolerance to IL-1 required a longer time to develop and was not complete. We investigated the possible roles of changes in serum corticosterone and glucose in the effects of LPS, TNF and IL-1. A single injection of LPS, TNF, or IL-1 markedly increased serum corticosterone levels after 2 h. After only 2 days of chronic treatment, mice given LPS or TNF were refractory to induction of serum corticosterone by a subsequent injection of LPS or TNF, but mice given IL-1 for 2 days were still fully responsive to IL-1.IL-1, unlike TNF and LPS, induced a marked hypoglycemic response. Repeated administration of IL-1 sensitized to its hypoglycemic effect. This lack of adaptation to the increase of serum corticosterone and hypoglycemia was also observed when IL-1 was given at lower, nonlethal doses (0.25-1.0-mu-g) and for a longer period (up to 8 days). The defective tolerance to the metabolic and toxic effects of IL-1 in this experimental model indicates that there are major differences between the in vivo biological responses to IL-1 and TNF.
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页码:1668 / 1672
页数:5
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