Researchers at Cornell University showed that giving mice the equivalent of six to eight cups of coffee a day protected them against experimental autoimmune encephalomyelitis (EAE), the animal model of MS. It is known that caffeine is a popular adenosine receptor blocker and the findings show that this molecule plays a vital role in permitting the infiltration of immune cells into the central nervous system of patients with MS.
Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that occurs when the body's immune system attacks and damages nerves in the brain and spinal cord. While the infiltration of immune cells into brain and other CNS tissue is a rare sight in healthy individuals without MS, the researchers are sure that the molecule adenosine is responsible for this infiltration.
Adenosine is widely present in the body and is vital to many biochemical processes, like energy transfer and the promotion of sleep and suppression of arousal.
Initial studies led the researchers to discover that mice lacking CD73, the enzyme necessary for synthesizing extracellular adenosine, were protected from developing the mouse form of MS (experimental autoimmune encephalomyelitis or EAE). Subsequent studies dealing with immune cells from such mice made them believe that normal CD73's ability to synthesize extracellular adenosine governed the development and progression of the MS-like disease.
Though this discovery did help the researchers to explain the presence of adenosine near the cells, but they were unaware of the mechanism that made the compound enter into the CNS cells. As adenosine is supposed to bind to its receptor in order to affect a cell, the researchers thought that adenosine receptor activation would have allowed for entry of immune cells into the brain and spinal cord and thus they turned to caffeine.
Caffeine's stimulatory effects on the CNS are mainly due to its ability to bind to the same receptors as adenosine, thus blocking adenosine's ability to affect CNS cells. When mice consumed caffeine in their drinking water, they were protected against development of EAE, the MS model.
Thus it was concluded that CD73 and adenosine receptor signalling are required for the efficient entry of immune cells into the CNS during the initiation and progression of EAE in mice and, quite possibly, during the development of MS in humans.
"These results might mark the first in a series of discoveries from our lab that could spawn the impetus for the development of adenosine-based therapies for the treatment of MS," said Bynoe.
The study was presented at Experimental Biology 2008 which was a part of the scientific programs of the American Society of Immunologists.