Intracerebroventricular interleukin-1beta impairs clearance of tumor cells from the lungs: role of brain prostaglandins.
We have previously demonstrated that central administration of interleukin (IL)-1beta suppresses natural killer (NK) cell activity, impairs NK-mediated lung clearance of tumor cells, and enhances tumor colonization. The central pathways activated by IL-1beta are as yet unknown. Using an in vivo model of tumor colonization, this study examined the role of central noradrenergic, opioid and prostaglandin mechanisms in mediating the effect of IL-1beta on lung clearance of tumor cells. We demonstrate that central noradrenergic and opioid systems are not critically involved in this effect. Neither depletion of central noradrenergic pathways, or administration of the opioid antagonist, naltrexone (50 ug), blocked the impaired lung clearance of MADB106 tumor cells induced by central administration of IL-1beta (20 ng). Central prostaglandins (PGs) do, however, appear to play a critical role. Central administration of the prostaglandin antagonist, diclofenac (250 ug), but not ibuprofen, completely blocked the effect of IL-1beta on lung clearance of tumor cells. Antagonism of the effects of IL-1beta was shown to be due to the effects of centrally and not of peripherally acting prostaglandins.
Hodgson
D M
DM
Laboratory of Neuroimmunology, School of Behavioural Sciences, University of Newcastle, Callaghan 2308, NSW, Newcastle, Australia. dhodgson@psychology.newcastle.edu.au
Yirmiya
R
R
Taylor
A N
AN
D000230:Adenocarcinoma / Q000473:pathology* / Q000503:physiopathology / Q000556:secondary; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000556:secondary; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009434:Neural Pathways / Q000503:physiopathology; D009638:Norepinephrine / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344
D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D009292:Narcotic Antagonists; D011453:Prostaglandins; D004008:Diclofenac; D009271:Naltrexone; D007052:Ibuprofen; D009638:Norepinephrine