中島 裕史

In a murine model of airway late phase reaction, we have previously shown that Ag-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4(+) T cells and IL-5. To determine whether IFN-alpha regulates Ag-induced eosinophil recruitment into tissue, we studied the effects of rIFN-alpha, endogenous IFN-alpha production induced by poly I.C, and anti-IFN-alpha mAb on the eosinophil infiltration of the trachea induced by Ag inhalation in mice. The i.p. administration of rIFN-alpha prevented Ag-induced eosinophil infiltration in the trachea of sensitized mice. In addition, the inhibitory effect of rIFN-alpha on Ag-induced eosinophil infiltration was not recovered by pretreatment with anti-IFN-gamma mAb. The administration of rIFN-alpha also inhibited Ag-induced CD4(+) T cell infiltration in the trachea. However, the administration of rIFN-alpha did not significantly affect blood eosinophil counts nor the number of blood and splenic CD4(+) T cells. On the other hand, pretreatment with anti-murine IFN-alpha mAb enhanced Ag-induced eosinophil and CD4(+) T cell infiltration in the trachea. Finally, endogenous IFN-alpha/beta production induced by poly I.C also inhibited Ag-induced eosinophil infiltration in the trachea and this inhibition of the eosinophil infiltration was abrogated by pretreatment with anti-IFN-alpha/beta mAb. These results indicate that IFN-alpha suppresses Ag-induced eosinophil and CD4(+) T cell recruitment into tissue.

To determine the role of vascular cell adhesion molecule 1 (VCAM-1)/very late activation antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM-1)/lymphocyte function-associated antigen 1 (LFA-1) interactions in causing antigen-induced eosinophil and T cell recruitment into the tissue, we studied the effect of the in vivo blocking of VCAM-1, ICAM-1, VLA-4, and LFA-1 by pretreatment with monoclonal antibodies (mAb) to these four adhesion molecules on the eosinophil and T cell infiltration of the trachea induced by antigen inhalation in mice. The in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, prevented antigen-induced eosinophil infiltration into the mouse trachea. On the contrary, the in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, increased blood eosinophil counts after antigen challenge, but did not affect blood eosinophil counts without antigen challenge in sensitized mice. Furthermore, the expression of VCAM-1 but not ICAM-1 was strongly induced on the endothelium of the trachea after antigen challenge. In addition, pretreatment with anti-IL-4 mAb decreased the antigen-induced VCAM-1 expression only by 27% and had no significant effect on antigen-induced eosinophil infiltration into the trachea. The in vivo blocking of VCAM-1 and VLA-4 inhibited antigen-induced CD4+ and CD8+ T cell infiltration into the trachea more potently than that of ICAM-1 and LFA-1. In contrast, regardless of antigen challenge, the in vivo blocking of LFA-1, but not of ICAM-1, increased blood lymphocyte counts more than that of VCAM-1 and VLA-4. These results indicate that VCAM-1/VLA-4 interaction plays a predominant role in controlling antigen-induced eosinophil and T cell recruitment into the tissue and that the induction of VCAM-1 expression on the endothelium at the site of allergic inflammation regulates this eosinophil and T cell recruitment.

A 44-year-old woman with scleroderma and Sjogren's syndrome developed altered consciousness, acute renal failure, and rhabdomyolysis. She had no history of trauma, seizures, alcohol abuse, hyperthermia, or other possible causative factors for rhabdomyolysis. A high serum salicylate level indicated a diagnosis of salicylate intoxication. Medical history after recovery revealed chronic salicylate ingestion for severe headaches. This is possibly the first reported case of rhabdomyolysis caused by chronic salicylate intoxication. Continuous hemodiafiltration early in hospitalization was an effective treatment.

We have previously shown that antigen-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4+ T cells and interleukin 5. To determine whether interferon gamma (IFN-gamma) regulates antigen-induced eosinophil recruitment into the tissue, we studied the effect of recombinant (r) murine IFN-gamma and of anti-IFN-gamma monoclonal antibody (mAb) on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. The intraperitoneal administration of rIFN-gamma prevented antigen-induced eosinophil infiltration in the trachea of sensitized mice. The administration of rIFN-gamma also decreased antigen-induced CD4+ T cell but not CD8+ T cell infiltration in the trachea. On the other hand, pretreatment with anti-IFN-gamma mAb enhanced antigen-induced eosinophil and CD4+ T cell infiltration in the trachea. These results indicate that IFN-gamma regulates antigen-induced eosinophil recruitment into the tissue by inhibiting CD4+ T cell infiltration.