Takumi Fukumoto

Administration of neutralizing antibody against rabbit IL-1 receptor antagonist exacerbates lipopolysaccharide-induced arthritis in rabbits

Endogenous IL-1 receptor antagonist (IL-1ra) may down-regulate part of IL-1 actions. We examined the participation of endogenous IL-1ra in the production of IL-1β in vitro. Macrophages cultured on adherent IgG produced a 100-fold molar excess of IL-1ra, compared with IL-1β. In the presence of a neutralizing monoclonal antibody (mAb) against rabbit IL-1ra, the production of antigenic IL-1β increased by 20–60%. Since the molar ratio of IL-1ra over IL-1 was 160- to 400-fold in synovial fluid (SF) of lipopolysaccharide (LPS)-induced arthritis, we examined the functional role of endogenous IL-1ra in the regulation of inflammatory responses. When measured in the presence of anti-IL-1ra mAb, masked IL-1 activity in SF became evident, with a 3- to 4-fold increment. The administration of anti-IL-1ra mAb with LPS into rabbit knee joints increased the IL-1 activity 4-fold and the production of antigenic IL-1β by 30–50%. The treatment also enhanced by 20–40% LPS-induced leukocyte infiltration and protein leakage. Therefore, endogenous IL-1ra apparently acts as a down-regulating factor for limiting delecterious effects of IL-1 by masking the biological activity and by inhibiting the production.

IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy.

We investigated the involvement of IL‐8 in the delayed vascular permeability (VP) in rabbit lipopolysaccharide (LPS)‐pleurisy. Maximal level of interleukin‐8 (IL‐8) was detected in pleural fluid at 2 h after LPS injection and anti‐IL‐8 inhibited the delayed VP by 90%. Injection of homologous IL‐8 induced VP, the time‐course of which preceded that of LPS‐induced delayed VP. Production of IL‐8 in LPS‐pleurisy was inhibited with anti‐tumor necrosis factor α (TNF‐α), whereas the production of TNF‐α was not affected with anti‐IL‐8. Injection of IL‐8 did not induce TNF‐α production and anti‐TNF‐α had no effect on IL‐8‐induced VP. Injection of homologous TNF‐α induced IL‐8 production and VP, and TNF‐α‐induced delayed VP was blocked with anti‐IL‐8. These results indicate important roles of IL‐8 in LPS‐induced delayed VP and that TNF‐α causes the delayed VP through the production of IL‐8. J. Leukoc. Biol. 63: 584–590; 1998.

Results of Surgical Treatment for Lumbosacral Radiculopathy of Lumbar Spinal Stenosis

This study investigated the operative results of the lumbosacral radiculopathy of lumbar canal stenosis. 24 cases were treated by surgery 9 cases received fenestration, 8 cases also received wide laminectomy, and in addition 7 cases received lumbar segmental fusion by instrumentation. The mean age at the time of surgery was 69.8 years (ragne; 56 to 81 years). The mean duration of follow-up was 23 months (range; 12 to 31 months).The clinical results were evaluated by the JOA score, and the recovery rate was determined by Hirabayashis method, and by the recovery ratio of radiculopathy symptoms, pain and dysesthesia of the lower extremities. The preoperative mean JOA score was 14.5 points, which changed to 20.5 points at the final check, and the mean recovery rate was 42.7%. The recovery ratio of radiculopathy pain shows a tendency to decrease as the number of decompressed intervertebral segments increase.