The main etiological factor responsible for irreversible pulpitis is advanced bacterial infection. Irreversible pulpitis occurs when the pulp tissue undergoes a severe inflammatory response that cannot be resolved, leading to persistent pain and irreversible damage to the pulp cells.

Key points to understand include:
- Advanced bacterial infection results from caries progression, allowing bacteria and their by-products to penetrate deeply into the pulp tissue.
- This infection triggers an intense inflammatory reaction with tissue necrosis and irreversible damage.
- Mechanical trauma and thermal irritation may contribute to pulpitis but are generally associated with reversible inflammation or transient pulpitis rather than irreversible changes.
- Mild reversible inflammation can typically heal once the irritant is removed, which contrasts with irreversible pulpitis where the pulp cannot recover spontaneously.

Therefore, the persistence of bacterial infection and the associated host immune response are the primary causes transforming pulp inflammation into the irreversible state.

Reference: Robinson's Current Therapy in Endodontics, Volume 1, Chapter 3, Page 45