title: Opiate modulation of IL-1alpha, IL-2, and TNF-alpha transport across the blood-brain barrier.
abstract: Interleukin-1alpha (IL-1alpha), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-alpha) are proinflammatory cytokines with potent neuromodulatory effects and are implicated in the etiology and pathogenesis of various psychological and neurological disorders. The findings that chronic morphine treatment alters both blood-brain barrier (BBB) function and cytokine production raises the possibility that morphine can also modulate cytokine transport across the BBB. Here, we found that acute morphine treatment (12 mg/kg i.p.) did not alter blood-to-brain transport of IL-1alpha, IL-2 or TNF-alpha. Whereas chronic morphine treatment (48 h after implantation of 75 mg morphine pellets) and withdrawal from morphine (10-15 min after an i.p. injection of 1mg/kg of naltroxone 48 h after implantation of 75 mg morphine pellets) did not alter blood-to-brain transport of IL-1alpha or TNF-alpha, both the chronic morphine treatment and withdrawal from morphine groups had increased blood-to-brain transport of IL-2. Typically, the permeability of the BBB to IL-2 is dominated by brain-to-blood efflux, with only limited blood-to-brain transport. Here, we found that chronic morphine and withdrawal from morphine did not alter brain-to-blood efflux, but induced a novel saturable blood-to-brain transport system. Whereas IL-1alpha, IL-2, and TNF-alpha are all proinflammatory cytokines, morphine exposure has individualized effects on their blood-to-brain transport.
authors.affiliation: GRECC, Veterns Affairs Medical Center-St. Louis and Division of Geriatrics, Department of Internal Medicine, Saint Louis University School of Medicine, C/O Dr. William Banks' Laboratory, 915 N, Grand Boulevard, St. Louis, MO 63106, USA. Electronic address: jlynch16@slu.edu.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Lynch
authors.affiliation: GRECC, Veterns Affairs Medical Center-St. Louis and Division of Geriatrics, Department of Internal Medicine, Saint Louis University School of Medicine, C/O Dr. William Banks' Laboratory, 915 N, Grand Boulevard, St. Louis, MO 63106, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D016207:Cytokines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D053582:Interleukin-1alpha / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D007376:Interleukin-2 / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000701:Analgesics, Opioid; D016207:Cytokines; D053582:Interleukin-1alpha; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D009020:Morphine