Alterations in cytokine/chemokine expression during organ-to-organ communication established via acetaminophen-induced toxicity.
A variety of studies have demonstrated that organ-to-organ communication circuits are established during various disease states. For example, an activated liver may release high levels of cytokines, which are carried to the lung and activate this organ. In the present study, we have examined the inflammation occurring as the liver-lung interact during the initiation of acetaminophen-induced toxicity. An overnight fast followed by an intraperitoneal acetaminophen challenge was required to elicit liver injury. In these animals, lung injury was most pronounced at 24 h post-challenge and was characterized by necrosis, edema and inflammation. Interestingly, the non-fasted/fed animals that received acetaminophen had only minor liver injury, but still presented with significant pathologic changes of the lung. BAL fluid contained increased neutrophils after acetaminophen challenge in the fasted (26%) and the fed (35%) animal groups. A significant vascular leak was found in the fasted, but not the fed, acetaminophen challenged animals. However, lung levels of the chemokine, eotaxin, and the cytokine, IL-12, were significantly elevated in the acetaminophen challenged animals that were fed, but not in the fasted group. The immunoneutralization of eotaxin, but not IL-12 or TNF-alpha, improved the histological appearance of the lung in fed mice challenged with acetaminophen.
Neff
Simona B
SB
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Neff
Thomas A
TA
Kunkel
Steven L
SL
Hogaboam
Cory M
CM
D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D005215:Fasting; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018712:Analgesics, Non-Narcotic; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D000082:Acetaminophen