The Effect of Intra-Articular Injection of Two Anti TNFα Drugs on Histopathology and Effect of Local Infusion of these Drugs on Blood Flow of Chronically Inflamed Joints in Rabbit

The anti TNFα drugs are new line treatment for articular inflammatory diseases which are used systemically, but due to expensiveness and some systemic adverse effects have limited usage. The aims of this study were to investigate the effect of intra-articular (local) injection of Etanercept and Infliximab as two anti TNFα drugs on histopathology and also due to the important role of joint blood flow on joint performance, to investigate the effect of local infusion of these drugs on blood flow of chronically inflamed joints.

Forty two NZW rabbits, underwent chronic knee joint inflammation by antigen induced arthritis method and then were randomly assigned into histopathology and blood flow groups. Each group was divided into 3 subgroups: vehicle (normal saline), Etanercept and Infliximab. In the first group, 2 weeks after intraarticular injection of antigen either 4 mg Etanercept, 16 mg Infliximab or o.5 ml vehicle was injected into the joint and after 2 weeks microscopic sections of knee joints were assessed for synovial membrane hyperplasia, villus hyperplasia, inflammatory cell infiltration and pannus formation. In the second group, 4 weeks after intraarticular injection of antigen, either 4 mg Etanercept, 1 mg Infliximab or vehicle was locally infused into articular atrery. Systemic blood pressure via carotid artery canulla and joint blood flow (JBF) by Laser Doppler Flowmeter were recorded.

Intraarticular injection of Etanercept and Infliximab had no significant effect on histopathological indices of inflammation. Etanercept increased JBF by 63.8±16.1% and decreased JVR by 42.2±4.4%. Infliximab, too, increased JBF by 70.6±16.1.1% and decreased JVR by 38.7 ±6.3%. The drugs had no effect on arterial blood pressure.

Although not significantly effective on histopathlogical indices, Etanercept and Infliximab seems to improve prognosis of chronic joint diseases such as rheumatoid arthritis through blood flow enhancement and hypoxia diminution.