Interleukin-10 inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin-1 beta production in the brain without affecting the activation of the hypothalamus-pituitary-adrenal axis.
Interleukin (IL) 10 inhibits endotoxin (lipopolysaccharide; LPS) induced tumor necrosis factor (TNF) production in vivo and in vitro. In turn, IL-10 is induced by LPS and acts as a negative feedback to limit TNF production. We investigated the effects of IL-10 on brain TNF and IL-1 beta production induced by a central LPS administration in mice. Because central LPS also induces peripheral TNF, we also measured the serum TNF levels. A single intracerebroventricular injection of murine recombinant IL-10 (75 ng/mouse) simultaneously with LPS (2.5 micrograms/mouse) almost completely inhibited brain TNF production. The brain IL-1 beta production was also inhibited, as was the serum concentration of the acute-phase protein serum amyloid A. On the other hand, intracerebroventricular administration of an anti-IL-10 monoclonal antibody (JES5-2A5; 60 micrograms/mouse) potentiated brain TNF and IL-1 beta production. Identical results were obtained when the serum TNF levels were measured. IL-10 did not affect the LPS-induced increase of serum corticosterone, the main endogenous inhibitor of TNF production, or the induction of IL-6. These results indicate that LPS-induced IL-10 can act as an important endogenous inhibitor of brain TNF production and suggest an anti-inflammatory role for IL-10 in the central nervous system.
Di Santo
E
E
Istituto di Ricerche Farmacologiche Mario Negri Milano, Italy.
Sironi
M
M
Pozzi
P
P
Gnocchi
P
P
Isetta
A M
AM
Delvaux
A
A
Goldman
M
M
Marchant
A
A
Ghezzi
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004731:Endotoxins / Q000494:pharmacology; D005246:Feedback; D005786:Gene Expression Regulation / Q000187:drug effects*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C044101:endotoxin, Escherichia coli; D003345:Corticosterone