title: Cachexia and the acute-phase protein response in inflammation are regulated by interleukin-6.
abstract: Cachexia and the acute-phase response are common manifestations of inflammation and are presumed to be the product of increased synthesis and release of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6). IL-1 receptor blockade has been previously shown to attenuate the weight loss, anorexia and acute-phase protein responses associated with a turpentine abscess. However, IL-1 receptor blockade was also associated with a reduced plasma IL-6 response, suggesting that the benefit achieved by IL-1 receptor blockade may be mediated by reduced systemic IL-6 production. To gain a better understanding of the role of IL-6 in this model of inflammation, C57BL/6 mice were passively immunized with either a monoclonal anti-IL-6 antibody (20F3), an anti-IL-1 type I receptor monoclonal antibody (35F5), a non-immune rat IgG, or a combined therapy of 35F5 and 20F3, before receiving a sterile turpentine abscess. IL-6 or IL-1 receptor blockade equally spared body weight and food intake. Compared to IL-1 receptor blockade, passive immunization against IL-6 further reduced the hepatic acute-phase protein response, as represented by serum amyloid P and complement 3. Combined blockade of IL-6 and IL-1 receptor did not result in a further sparing of body weights or improvement of food intake. These results confirm that IL-1 contributes to host cachexia and the acute-phase response following a turpentine abscess, but also show that these actions are dependent upon an IL-6 response. We conclude that the influence of IL-1 on cachexia and the acute-phase response is mediated, at least in part, through IL-6 and, thus, IL-6 may play a pivotal role in the cachexia and acute-phase response to inflammation.
authors.affiliation: Department of Surgery, Cornell University Medical College, New York, NY 10021.
authors.forename: H S
authors.initials: HS
authors.lastname: Oldenburg
authors.forename: M A
authors.initials: MA
authors.lastname: Rogy
authors.forename: D D
authors.initials: DD
authors.lastname: Lazarus
authors.forename: K J
authors.initials: KJ
authors.lastname: Van Zee
authors.forename: B P
authors.initials: BP
authors.lastname: Keeler
authors.forename: R A
authors.initials: RA
authors.lastname: Chizzonite
authors.forename: S F
authors.initials: SF
authors.lastname: Lowry
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000210:Acute-Phase Reaction / Q000209:etiology*; D000818:Animals; D002100:Cachexia / Q000209:etiology*; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000503:physiopathology*; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000502:physiology; D014425:Turpentine; D015431:Weight Loss
chemical_list: D007074:Immunoglobulin G; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D014425:Turpentine