In rheumatoid arthritis, a person's own immune system attacks the joints by activating the synovial tissue that lines the body's movable joints, causing inflammation, swelling, pain and eventually erosion of the bone and cartilage and deformation of the joint.
It is among the most debilitating forms of arthritis, often making difficult even the simplest of daily activities.
In a study presented April 29 at Experimental Biology 2007, University of Michigan Medical School scientist Dr. Salah-uddin Ahmed reports that a compound derived from green tea was able to inhibit production of several immune system molecules involved in inflammation and joint damage. The compound, named epigallocatechin-3-gallate (EGCG), an active principal of green tea extract, is a potent anti-inflammatory molecule, and also was able to inhibit production of interleukin-6 (IL-6) and prostaglandin E2, the inflammatory products found in the connective tissue of people with rheumatoid arthritis.
Dr. Ahmed's Experimental Biology presentation was part of the scientific program of the American Society for Nutrition.
Synovial fibroblasts (cells that form a lining of synovial tissue surrounding the capsule of the joints) were isolated from the joints of the patients suffering from rheumatoid arthritis, cultured in growth medium, and incubated with EGCG. Synovial fibroblasts were then stimulated with pro-inflammatory cytokine IL-1, a protein of the immune system known to play an important role in causing joint destruction in rheumatoid arthritis.
In an earlier study published by Dr. Ahmed's research group last fall, the researchers showed some interesting and novel findings when EGCG pretreated synovial fibroblasts were stimulated with the cytokine IL-1, to study the protective effect of this green tea compound. Compared to untreated synovial fibroblasts, the cells treated with EGCG markedly blocked IL-1s ability to produce the proteins and enzymes that infiltrate the joints of persons with rheumatoid arthritis causing cartilage degradation.
The scientists decided to extend their study to see if the green tea compound also has the capability to block the activity of two other potent molecules, IL-6 and cyclooxygenase-2 (COX-2), actively involved in causing bone erosion in the RA joint. In the new study presented at Experimental Biology, the scientists once again isolated synovial fibroblasts taken from the joints of patients suffering from rheumatoid arthritis and incubated these cells with the green tea compound. When untreated cells were stimulated with IL-1, a sequence of molecular events occurred that resulted in production of the bone-destructive molecules. But the scientists found that pre-incubation with EGCG was capable of blocking the production of these molecules in a dose-dependent manner. Furthermore, EGCG also inhibited the production of prostaglandin E2, which causes inflammation in the joints.
The cell signaling pathways that regulate levels of these immune system molecules under both normal and rheumatoid arthritis situations is well established, and the researchers were able to trace the effects of the green tea compound infusion to see that it worked by inhibiting these pathways.
Dr. Ahmed says that these studies suggest that EGCG or molecules that could be derived synthetically from the EGCG found in green tea may be of therapeutic value in inhibiting the joint destruction in this challenging disease. The laboratory now is focused on the inhibitory role of EGCG in gene expression. The scientists plan to give EGCG orally to mice genetically bred to be animal models of rheumatoid arthritis to see if it provides similar therapeutic or preventive effects. Dr. Ahmed believes these studies will form a strong foundation for future testing of green tea compounds in humans with rheumatoid arthritis.