Prednisolone promotes remission and gastric mucosal regeneration in experimental autoimmune gastritis.

Abstract

A cardinal feature of organ-specific autoimmunity is destructive pathology in the target organ. In human and experimental models of autoimmune gastritis, mononuclear cell infiltration and cellular destruction in the gastric mucosa are disease hallmarks. Strategies to cure autoimmune disease must not only establish immunological tolerance to autoantigen, but also rid the organ of pathogenic autoreactive cells. The present study has assessed the effect of prednisolone treatment in clearing the inflammatory infiltrate in experimental autoimmune gastritis and in preventing disease relapse in athymic compared with euthymic mice. Experimental autoimmune gastritis was induced by neonatal thymectomy or by transgenic expression of GM-CSF (PC-GMCSF mice). Groups of mice were treated with prednisolone (10 mg/kg per day) for 10 weeks or with prednisolone for 10 weeks followed by 10 weeks without prednisolone. Stomachs were examined for gross morphological changes, and by histology and immunohistochemistry for composition of inflammatory infiltrate and gastric mucosal integrity. Autoantibody to gastric H+/K+ ATPase was determined by ELISA. Prednisolone promoted remission of gastritis in both mouse models of experimental autoimmune gastritis, evident by reduction in stomach size, clearing of gastric inflammatory infiltrate, and regeneration of the gastric mucosa. Prednisolone withdrawal resulted in disease relapse in all PC-GMCSF mice, whereas approximately 40% of neonatal thymectomy mice retained normal stomach morphology and remained free of gastric pathology. It is concluded that prednisolone promotes remission and gastric mucosal regeneration in experimental autoimmune gastritis. Prolonged remission of autoimmune gastritis in some athymic mice suggests a role for the thymus in disease relapse.

• Authors: M Biondo, J Field, B-H Toh, F Alderuccio
• Journal: The Journal of pathology (J Pathol) Vol. 209 Issue 3 Pg. 384-91 (Jul 2006) ISSN: 0022-3417 [Print] England
• PMID: 16710833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2006 Pathological Society of Great Britain and Ireland.

Chemical References

• Anti-Inflammatory Agents
• Autoantibodies
• Glucocorticoids
• Granulocyte-Macrophage Colony-Stimulating Factor
• Prednisolone
• H(+)-K(+)-Exchanging ATPase

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Autoantibodies (biosynthesis)
• Autoimmune Diseases (drug therapy, immunology, pathology)
• CD4-Positive T-Lymphocytes (drug effects, immunology)
• Gastric Mucosa (immunology, pathology, physiology)
• Gastritis (drug therapy, immunology, pathology)
• Glucocorticoids (therapeutic use)
• Granulocyte-Macrophage Colony-Stimulating Factor (genetics)
• H(+)-K(+)-Exchanging ATPase (immunology)
• Lymphocyte Count
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Prednisolone (therapeutic use)
• Recurrence
• Regeneration
• Thymectomy