Early pregnancy factor suppresses the infiltration of lymphocytes and macrophages in the spinal cord of rats during experimental autoimmune encephalomyelitis but has no effect on apoptosis

• Published in: Journal of the neurological sciences Vol. 214; no. 1; pp. 27 - 36
• Main Authors: Athanasas-Platsis, Stavrosia, Zhang, Bing, Hillyard, Narelle C., Cavanagh, Alice C., Csurhes, Peter A., Morton, Halle, McCombe, Pamela A.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.10.2003; Elsevier Science
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - immunology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Cell Division - drug effects; Cell Division - immunology; Chaperonin 10; Chemotaxis, Leukocyte - drug effects; Chemotaxis, Leukocyte - immunology; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Down-Regulation - immunology; Early pregnancy factor; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - physiopathology; Experimental autoimmune encephalomyelitis; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Lymphocytes; Macrophages; Macrophages - drug effects; Macrophages - immunology; Male; Medical sciences; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Multiple Sclerosis - physiopathology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Myelin Basic Protein; Neurology; Peptides - pharmacology; Peptides - therapeutic use; Pregnancy Proteins; Rats; Rats, Inbred Lew; Reaction Time - drug effects; Reaction Time - immunology; Spinal cord; Spinal Cord - drug effects; Spinal Cord - immunology; Spinal Cord - physiopathology; Suppressor Factors, Immunologic; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Early pregnancy factor; Multiple sclerosis; Spinal cord; Lymphocytes; Experimental autoimmune encephalomyelitis; Macrophages; Apoptosis; Animal model; Nervous system diseases; Pathophysiology; Rat; Rodentia; Inflammatory disease; Vertebrata; Mammalia; Animal; Central nervous system disease; Lymphocyte; Macrophage
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/S0022-510X(03)00170-9

Early pregnancy factor (EPF) is a secreted protein with immunosuppressive and growth factor properties that has been shown to suppress acute experimental autoimmune encephalomyelitis (EAE) induced with myelin basic protein (MBP) in Lewis rats. EAE is associated with infiltration of the central nervous system (CNS) with inflammatory cells. Spontaneous recovery involves the loss of T lymphocytes from the CNS and the selective apoptosis of Vβ8.2 + cells. In the present study, T cell, macrophage (CD11b/c +) and B cell (CD45RA +) populations in spinal cord and popliteal lymph nodes (LN) of Lewis rats with EAE were quantitated and apoptosis was studied. Rats were treated with EPF or vehicle. Following treatment on day 14 after inoculation with MBP, neither 1×100 μg nor 2×100 μg doses of EPF affected the total number of cells infiltrating the spinal cord on day 15, although the higher dose caused a decrease in the number of CD5 + and CD11b/c + cells. Treatment with 2×100 μg/day from days 10 to 14 decreased the total number of infiltrating cells, and the numbers of CD5 +, CD11b/c + and CD45RA + cells. Apoptosis was unaffected. No alteration on the number or type of inflammatory cells in the popliteal LN was observed after treatment on days 10–14. However, treatment with EPF from days 0 to 11 increased the total number of T and B cells and CD5 + T cells found on day 12 in the LN. Similarly, there was an increase in the frequency of MBP-reactive cells in the LN as determined by limiting dilution analysis. These results suggest that EPF treatment reduces the numbers of lymphocytes and macrophages in the CNS, possibly through an effect on cell trafficking.