alexa Mechanism of action of methotrexate: experimental evidence that methotrexate blocks the binding of interleukin 1 beta to the interleukin 1 receptor on target cells.
Immunology

Immunology

Rheumatology: Current Research

Author(s): Brody M, Bhm I, Bauer R

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Abstract Interleukin 1, a multifunctional cytokine, plays a central role in inflammatory processes and induction of the immune response. Target cells possess 200-5000 (or more) interleukin 1 receptors per cell, but they exhibit a full biological response when only 1-2\% of these receptors are occupied by interleukin 1 alpha or 1 beta. Methotrexate has been reported to be beneficial in several inflammatory and autoimmune diseases. On the other hand, many of these diseases are known to share an overproduction of interleukin 1. It has been demonstrated that methotrexate has no influence on the interleukin 1 synthesis, so we focused our attention on the ability of methotrexate to interfere with the binding of interleukin 1 beta to the interleukin 1 receptor. The experiments were performed on monocytes, lymphocytes and granulocytes using a recombinant human cytokine probe. Methotrexate led to an astonishing decrease in the binding of interleukin 1 beta to the interleukin 1 receptor of peripheral blood cells, whereas methylprednisolone and indomethacin were not inhibitory. The inhibitory effect of methotrexate was dose dependent. An excess of interleukin 1 beta abolished the inhibition of cytokine binding by methotrexate. We also demonstrated that methotrexate does not affect the integrity of the interleukin 1 receptor or of the target cells. Our results demonstrate that methotrexate blocks the interleukin 1 beta-interleukin 1 receptor pathway. Methotrexate is therefore another interleukin 1 inhibitor and a clinically efficient anticytokine.
This article was published in Eur J Clin Chem Clin Biochem and referenced in Rheumatology: Current Research

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