Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study

Area of Science:

• Immunology
• Transplantation Medicine
• Pharmacology

Background:

• Sirolimus, an immunosuppressant, poses challenges in kidney transplantation due to frequent side effects.
• Paradoxical inflammatory manifestations are common but their pathophysiology is unclear.

Purpose of the Study:

• To investigate the pathophysiology of sirolimus-induced inflammatory side effects.
• To analyze the impact of switching to sirolimus on inflammatory markers and symptoms.

Main Methods:

• Prospective follow-up of 30 kidney transplant recipients switching to sirolimus.
• Quantification of inflammatory symptoms using visual analogue scales.
• Serum sample analysis for biochemical and cytokine profiles at multiple time points.

Main Results:

• 66% of patients reported inflammatory symptoms, primarily cutaneo-mucosal.
• Biochemical changes included decreased hemoglobin and increased acute phase proteins.
• Sirolimus increased IL-6 and TNF-α, without compensatory IL-10, correlating with inflammation.

Conclusions:

• Sirolimus destabilizes the inflammatory cytokine balance, causing paradoxical inflammation.
• This mechanism explains the varied inflammatory side effects observed with sirolimus.
• Sirolimus-induced inflammatory events may represent a single syndromic entity.