Splenectomy attenuates streptococcal cell wall-induced arthritis and alters leukocyte activation.
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.


CONCLUSIONS
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.
Kimpel
Donald
D
Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA. dlk9t@hscmail.mcc.virginia.edu
Dayton
Tim
T
Fuseler
John
J
Gray
Laura
L
Kannan
Krishnaswamy
K
Wolf
Robert E
RE
Grisham
Matthew
M
D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D015415:Biomarkers; D019070:Cell Lineage / Q000276:immunology; D002473:Cell Wall / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D005260:Female; D018960:Hyaluronan Receptors / Q000378:metabolism; D007596:Joints / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology / Q000601:surgery; D013156:Splenectomy; D013290:Streptococcal Infections / Q000276:immunology* / Q000601:surgery*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D018960:Hyaluronan Receptors; D009566:Nitrates; D009573:Nitrites