Tesis

Efek Imunomodulasi Sekretom Sel Punca Mesenkim Asal Tali Pusat terhadap Pola Mediator Pro- dan Anti-Inflamasi: Kajian terhadap Komponen sIL-6R, sgp130 dan IL-1RA Pada Kultur Darah Pasien COVID-19 = Immunomodulation Effect of Umbilical Cord Mesenchymal Stem Cell-derived Secretome on The Pro- and Anti-Inflammatory Mediator Patterns: Study on sIL-6R, sgp130, and IL-1RA in Blood Culture of Severe COVID-19 Patients.

COVID-19 disebabkan oleh infeksi SARS-CoV-2 hadir dengan manifestasi klinis beragam dari tanpa gejala hingga menunjukkan gejala berat. Tingkat keparahan COVID-19 dikaitkan dengan peningkatan kadar mediator inflamasi yang tidak terkontrol. Hingga saat ini belum ada pengobatan yang sangat efektif untuk COVID-19. Efek immunomodulasi SPM yang diperankan oleh sekretom mulai dikembangkan sebagai terapi COVID-19. Namun demikian, penggunaan sekretom secara tunggal dinilai lebih aman apabila dibandingkan dengan SPM karena dapat memperkecil efek terapi berbasis sel. Mekanisme immunomodulasi sekretom sebagai agen terapi COVID-19 masih belum dipahami secara jelas sampai sekarang. Penelitian ini bertujuan menganalisis pengaruh pemberian sekretom SPM-TP terhadap produksi mediator pro dan anti-inflamasi dengan mengkaji peran sIL-6R, sgp130 dan IL-1RA pada kultur darah lengkap subyek COVID-19 derajat berat. Sebanyak 12 sampel darah subyek COVID-19 derajat berat dikultur ke dalam tiga kelompok perlakuan (kelompok kontrol negatif, kelompok kontrol positif LPS dan kelompok stimulasi sekretom 3µL) yang diinkubasi selama 24 dan 72 jam. Supernatan kultur pada masing-masing waktu inkubasi dipanen dan diukur kadar sIL-6R, sgp130, IL-1RA, IL-6, TNF-α, IFN-γ dan IL-10. Pemberian sekretom SPM-TP mempengaruhi pola produksi mediator pro-inflamasi (IL-6, TNF-α) dan anti-inflamasi (IL-10) secara signifikan, namun tidak pada IFN-γ. Perubahan produksi mediator tersebut dipengaruhi secara signifikan oleh peningkatan produksi IL-1RA.
Kata kunci: COVID-19, sekretom, sIL-6R, sgp130, IL-1RA


COVID-19, caused by infection with SARS-CoV-2 presents with clinical manifestations ranging from asymptomatic to severe symptoms. The severity of COVID-19 is associated with uncontrolled elevated levels of inflammatory mediators. There is currently no highly effective treatment for COVID-19. The immunomodulating effect of MSCs mediated by secretomes has begun to be developed as a COVID-19 therapy. However, the use of secretome alone is considered safer when compared to MSC because it can minimize the effects of cellbased therapy. The mechanism of secretome immunomodulation as a therapeutic agent for COVID-19 was not clearly understood until now. This study aimed to analyze the effect of administration of UC-MSC-derived secretome on the production of pro and anti-inflammatory mediators by examining the roles of sIL- 6R, sgp130, and IL-1RA in whole blood cultures of severe COVID-19 subjects. A total of 12 blood samples of severe COVID-19 subjects were cultured into three groups (negative control group, LPS positive control group, and 3µL secretome stimulation group), which were incubated for 24 and 72 hours. The culture supernatants at each incubation time were harvested and the levels of sIL-6R, sgp130, IL-1RA, IL-6, TNF-α, IFN-γ, and IL-10 were measured. Stimulation of the UC-MSC-derived secretome affects the pattern of production of pro-inflammatory mediators (IL-6, TNF-α) and anti-inflammatory (IL-10) significantly, but not on IFN-γ. Changes in the production of these mediators were significantly affected by the increased production of IL-1RA.
Keywords: COVID-19, secretome, sIL-6R, sgp130, IL-1RA.