Methotrexate can be used to control the autoimmune attack and auto-inflammatory response in rheumatoid arthritis.  It has a number of mechanisms of action, including increasing adenosine levels. How does increasing adenosine levels help to combat autoimmune and auto-inflammatory attack on the joints? 

Let’s first dispel a potential misunderstanding. Adenosine is not the same thing as adenine.  If we confuse adenosine with adenine, then it may appear contradictory that the mechanisms of action of methotrexate include both increasing adenosine levels and reducing pyrimidine levels. There is no contradiction here. Adenine and guanine are purines. Purines and pyrimidines are nitrogenous bases required for the nucleotide building blocks of DNA. Thus depletion of pyrimidines with drugs such as methotrexate and leflunomide or depletion of purines, including adenine, with drugs such as azathioprine and mycophenolate can interfere with DNA synthesis and proliferation of immune system and inflammatory cells.

Adenosine is a purine nucleoside composed of a molecule of adenine attached to a ribose sugar molecule.  It is a ribonucleoside necessary for the synthesis of RNA but has many other cellular functions as well. Adenosine triphosphate (ATP) is, of course, well-known as the cellular energy currency.  Adenosine itself is also a transmitter acting at adenosine receptors. Adenosine signalling suppresses recruitment and functions of inflammatory and immune cells. Thus increasing adenosine levels has an anti-inflammatory and immunosuppressant effect.