A 50-year-old woman with rheumatoid arthritis is started on methotrexate. What is the primary mechanism by which methotrexate exerts its therapeutic effects?
- A) Inhibition of dihydrofolate reductase ✓
- B) Stimulation of leukocyte production
- C) Suppression of tumor necrosis factor-alpha (TNF-alpha)
- D) Inhibition of cyclooxygenase enzymes
Methotrexate is a cornerstone medication used in the treatment of rheumatoid arthritis (RA) and other autoimmune diseases. Understanding its primary mechanism of action is crucial for appreciating how it helps manage these conditions.
Step 1: Overview of Methotrexate
Methotrexate is an antimetabolite and immunosuppressive agent that has been widely used since the 1980s for treating RA. It works by interfering with various cellular processes, particularly those involved in DNA synthesis and cell proliferation.
Step 2: Mechanism of Action
The primary mechanism by which methotrexate exerts its therapeutic effects is through the inhibition of dihydrofolate reductase (DHFR). This enzyme plays a critical role in the folate metabolism pathway, which is essential for the synthesis of nucleotides necessary for DNA replication and repair. By inhibiting DHFR, methotrexate effectively reduces the availability of tetrahydrofolate, leading to decreased production of purines and pyrimidines. This results in reduced lymphocyte proliferation and ultimately dampens the immune response that characterizes rheumatoid arthritis.
Step 3: Comparison with Other Options
- B) Stimulation of leukocyte production: This option is incorrect as methotrexate does not stimulate leukocyte production; rather, it suppresses excessive immune activity.
- C) Suppression of tumor necrosis factor-alpha (TNF-alpha): While methotrexate may have some indirect effects on TNF-alpha levels, this is not its primary mechanism. TNF-alpha inhibitors are a separate class of medications specifically targeting this cytokine.
- D) Inhibition of cyclooxygenase enzymes: This option refers to nonsteroidal anti-inflammatory drugs (NSAIDs), which work differently than methotrexate. Methotrexate does not primarily function through cyclooxygenase inhibition.
Given this analysis, it becomes clear that the correct answer regarding the primary mechanism by which methotrexate exerts its therapeutic effects in rheumatoid arthritis is:
A) Inhibition of dihydrofolate reductase
