Tofacitinib is a Janus kinase inhibitor. JAK proteins are intracellular enzymes that transmit signals from a variety of cytokine receptors to the cell nucleus.
Tofacitinib inhibits JAK-dependent signaling and thereby reduces signaling from cytokines involved in immune-cell activation and inflammatory responses. The medicine has functional selectivity for JAK1 and JAK3 over JAK2 at therapeutic concentrations, although its pharmacology involves more than a single pathway.
Simple explanation
Many inflammatory diseases involve excessive or persistent immune signaling. Cytokines act as chemical messengers that tell immune cells how to behave.
Tofacitinib interferes with part of the intracellular signaling system used by these messengers. The result is reduced activity in several inflammatory pathways.
Detailed mechanism
The JAK-STAT pathway is an important signaling mechanism. Cytokine receptor activation can activate JAK enzymes, which then phosphorylate signal transducers and activators of transcription, or STAT proteins. STAT proteins influence gene expression after moving into the nucleus.
Tofacitinib reduces signaling through selected JAK pathways. This broad pathway effect helps explain its activity across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and ulcerative colitis.
Why immune suppression matters
The same immune-modulating activity that can reduce inflammation can also reduce protective immune responses. This is why serious infections, tuberculosis, malignancy and other risks are important parts of tofacitinib safety monitoring.