title: Role of TNF alpha, IL-1, and IL-1ra in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy.
abstract: We examined the generation of tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1), and IL-1 receptor antagonist (IL-1ra), and their role in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy. The leukocyte infiltration was largely mediated by both TNF alpha and IL-1 and could be divided into at least two phases: the early (within 3 hr) phase which was partly inhibited by anti-TNF alpha, but not by IL-1ra, and the late phase (4-12 hr) mediated by both TNF alpha and IL-1, and largely inhibited synergistically with anti-TNF alpha and IL-1ra. Endogenous IL-1ra may be responsible for the downregulation of the late phase of leukocyte infiltration in this type of inflammation. The increased vascular permeability was composed of two phases: immediate (15 min) and delayed (2 hr). The immediate permeability was inhibited by H1-antihistamine but was not affected by anti-TNF alpha, by IL-1ra, or by depletion of neutrophils. The delayed permeability was completely inhibited by either depletion of neutrophils or by anti-TNF alpha and was not affected by IL-1ra or antihistamine. Production of TNF alpha was maintained in the leukopenic rabbits. It would thus appear that the delayed permeability is mediated by a relatively early fraction of leukocyte infiltration initiated by TNF alpha; however, TNF alpha is not the direct mediator of this delayed permeability.
authors.affiliation: Department of Pathology, Kumamoto University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Edamitsu
authors.forename: A
authors.initials: A
authors.lastname: Matsukawa
authors.forename: S
authors.initials: S
authors.lastname: Ohkawara
authors.forename: K
authors.initials: K
authors.lastname: Takagi
authors.forename: H
authors.initials: H
authors.lastname: Nariuchi
authors.forename: M
authors.initials: M
authors.lastname: Yoshinaga
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008070:Lipopolysaccharides; D010994:Pleura / Q000166:cytology; D010998:Pleurisy / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D014311:Triprolidine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
chemical_list: D000906:Antibodies; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D014311:Triprolidine