Role of TNFα, IL-1, and IL-1ra in the Mediation of Leukocyte Infiltration and Increased Vascular Permeability in Rabbits with LPS-Induced Pleurisy

Sunao Edamitsu, Akihiro Matsukawa, Susumu Ohkawara, Katsumasa Takagi, Hideo Nariuchi, Masaru Yoshinaga

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We examined the generation of tumor necrosis factor-α (TNFα), 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 TNFα and IL-1 and could be divided into at least two phases: the early (within 3 hr) phase which was partly inhibited by anti-TNFα, but not by IL-1ra, and the late phase (4-12 hr) mediated by both TNFα and IL-1, and largely inhibited synergistically with anti-TNFα 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-TNFα, by IL-1ra, or by depletion of neutrophils. The delayed permeability was completely inhibited by either depletion of neutrophils or by anti-TNFα and was not affected by IL-1ra or antihistamine. Production of TNFα 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 TNFα; however, TNFα is not the direct mediator of this delayed permeability.

Original languageEnglish
Pages (from-to)68-74
Number of pages7
JournalClinical Immunology and Immunopathology
Volume75
Issue number1
DOIs
Publication statusPublished - Apr 1995
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology

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