Splenectomy Attenuates Streptococcal Cell Wall-Induced Arthritis and Alters Leukocyte Activation

Arthritis Rheum. 2003 Dec;48(12):3557-67. doi: 10.1002/art.11424.

Abstract

Objective: To investigate the role of the spleen in the pathogenesis of streptococcal cell wall (SCW)-induced arthritis and determine the impact of splenectomy on monocytes and T cells involved in the arthritis.

Methods: Female Lewis rats were separated into 4 groups: 1) saline-injected, sham-operated; 2) saline-injected, splenectomized; 3) peptidoglycan-polysaccharide (PG-PS)-injected, sham-operated; and 4) PG-PS-injected, splenectomized. After a 10-day recovery period, rats received a single intraperitoneal injection of saline or PG-PS (25 microg rhamnose/gm body weight). We evaluated the effect of splenectomy on joint inflammation, histopathology, leukocyte subtypes in blood and lymph nodes, cytokines, and cell surface expression of CD44 and CD45RC in the chronic phase of the disease (day 28).

Results: Splenectomy dramatically decreased chronic joint inflammation and histopathologic damage as well as altered cell types in lymph nodes and peripheral blood, as analyzed by flow cytometry. Nitric oxide (NO) production, levels of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha, and a biomarker of Th1 cell predominance correlated with the level of joint inflammation. Surprisingly, in splenectomized animals, increased expression of adhesion molecules thought to track T cells to inflamed tissue were observed in lymph nodes.

Conclusion: The result of splenectomy was attenuation of SCW-induced arthritis and changes in mediators of inflammation, including T cell subsets, proinflammatory cytokines, and NO production. Splenectomy may remove an important antigen reservoir and alter immune cell activation in the SCW-induced arthritis model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis, Infectious / immunology*
  • Arthritis, Infectious / pathology
  • Arthritis, Infectious / surgery*
  • Biomarkers
  • Cell Lineage / immunology
  • Cell Wall / immunology
  • Chronic Disease
  • Cytokines / metabolism
  • Female
  • Hyaluronan Receptors / metabolism
  • Joints / pathology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology
  • Nitrates / blood
  • Nitrites / blood
  • Rats
  • Rats, Inbred Lew
  • Spleen / immunology
  • Spleen / surgery
  • Splenectomy*
  • Streptococcal Infections / immunology*
  • Streptococcal Infections / surgery*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Hyaluronan Receptors
  • Nitrates
  • Nitrites