Impact of Lymphatic Pump Treatment and Methotrexate on Inflammation, Cytokine Production, and Leukocyte Infiltration in a Rat Model of Rheumatoid Arthritis

Abstract Rheumatoid Arthritis in autoimmune disease afflicting synovial joints leading to chronic joint damage. While the specific mechanisms have not been fully identified, the immune system and inflammatory factors are actively involved. T cells release cytokines and chemokines, such as TNF-alpha, IL-1 and IL-6, CINC-1 and CINC-2, and B cells produce self-reactive antibodies including rheumatoid factor and anti-citrullinated protein antibodies. All these factors result in a pronounced and aggressive inflammatory response within the joints. Lymphatic pump treatment (LPT) promotes lymphatic flow within the body, causing a flushing out of the immune-complexes and pro-inflammatory cells. Using a rat AIA model, the goal was to determine if LPT in conjunction with methotrexate had a greater impact on rheumatoid arthritis symptoms than methotrexate alone. A 21-day AIA rat study was performed using LPT and methotrexate treatments on days 14–21. Ankle circumference and articular index scores were recorded daily as a measurement of inflammation. ELISAs of arthritic ankles homogenates and serum were used to analyze cytokine, chemokine, and autoantibody concentrations. Immune cell infiltration into the ankles was determined using immunohistochemistry. We found that LPT with methotrexate treatment did not significantly alter ankle circumference, articular index scores, immune cell infiltration, cytokine, chemokine, or antibody concentrations compared to methotrexate alone. Overall, methotrexate combined with LPT treatments on days 14–21 did not significantly alter disease progression, however, it is possible that earlier LPT treatment may have a more significant impact on disease progression. College of Graduate Studies Biomedical Sciences program at Midwestern University, Downers Grove, IL.