Bacterial lipopolysaccharide induction of IL-6 in rat telencephalic cells is mediated in part by IL-1.
Interleukin-6 (IL-6) appears in the cerebrospinal fluid (CSF) of patients with acute infection of the central nervous system, and in the brains and CSF of experimental animals following systemic or intracerebral injection of bacterial endotoxin (Escherichia coli lipopolysaccharide, LPS). Since LPS is known to induce secretion of interleukin-1 (IL-1) in many cell types including those of the brain, and IL-1 can induce IL-6 in brain tissue it appeared reasonable to postulate that the effects of LPS on IL-6 production were mediated through IL-1 induction. To test this hypothesis, the effects of IL-1 receptor antagonist (IL-1Ra) on LPS and IL-1-induced IL-6 secretion were tested in a mixed brain cell culture from 17-day fetal rat, after 12-14 days in culture. IL-6 secretion was induced by IL-1 beta in a concentration as low as 1 x 10(-10) M (p = 0.0008); addition of IL-1Ra was shown to inhibit IL-1-induced changes by 87% (p = 0.0012) at a molar ratio of 100:1, and by 100% at a molar ratio of 1,000:1, LPS stimulated IL-6 secretion progressively over the concentration of 1-100 ng/ml (p = 0.0001). LPS 10 ng/ml-induced IL-6 secretion was inhibited by 66% by IL-1Ra in a concentration of 1,000 ng/ml (p = 0.0077). The inhibitory effect of IL-1Ra was not significantly greater even when used at a concentration of 5,000 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Romero
L I
LI
Division of Endocrinology, New England Medical Center, Boston, Mass. 02111.
Schettini
G
G
Lechan
R M
RM
Dinarello
C A
CA
Reichlin
S
S
D000818:Animals; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013687:Telencephalon / Q000166:cytology / Q000378:metabolism*
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1