Intracerebroventricular interleukin-1 beta impairs clearance of tumor cells from the lungs: role of brain prostaglandins

We have previously demonstrated that central administration of interleukin (IL)-1 beta suppresses natural killer (NK) cell activity, impairs NK-mediat ed lung clearance of tumor cells, and enhances tumor colonization. The cent ral pathways activated by IL-1 beta are as yet unknown. Using an in vivo mo del of tumor colonization. this study examined the role of central noradren ergic, opioid and prostaglandin mechanisms in mediating the effect of IL-1 beta on lung clearance of tumor cells. We demonstrate that central noradren ergic and opioid systems are not critically involved in this effect. Neithe r depletion of central noradrenergic pathways, or administration of the opi oid antagonist, naltrexone (50 ug), blocked the impaired lung clearance of MADB106 tumor cells induced by central administration of IL-1 beta (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-1 beta on lung cle arance of tumor cells. Antagonism of the effects of IL-1 beta was shown to be due to the effects of centrally and not of peripherally acting prostagla ndins. (C) 2001 Elsevier Science B.V. All rights reserved.