PhD Scientific Days 2022

Translational Medicine III.

The role of complement activation in cytokine release of human PBMC cells

Text of the abstract

Unregulated secretion of cytokines is called cytokine storm (CS), which can be life threatening and occasionally lethal as seen in COVID-19 patients. The vaccines designed to prevent or mitigate COVID-19 symptoms can cause allergic symptoms although these reactions are very rarely severe. Complement activation is an integral part of the immune defense against infections, but the role of the anaphylatoxins in cytokine release is not yet known.

Our main goal was to reveal the role of the complement activation on COVID-19 vaccines-induced cytokine release by human immune cells.

Human peripheral blood mononuclear cells (PBMC) of healthy donors were cultured in a medium containing 20 % autologous serum, and were treated with 50 µl undiluted Pfizer or AstraZeneca vaccines (250 µl total volume). The complement system was inhibited using C1 esterase (C1-INH; Berinert) and C5a/C5b (Eculizumab) inhibitors or by heat inactivation of serum. Cytokine concentrations were measured using ELISA 18 hours after treatments.

The vaccines caused minimal changes in IL-1α concentrations. INFγ concentrations were low in Pfizer vaccine -treated but were high in AstraZeneca vaccine-treated samples. Pfizer vaccine induced limited IL-1β and TNFα secretion but AstraZeneca vaccine caused massive rise in their concentrations. Both vaccines induced marked changes in IL-6 release. Pfizer had huge but AstraZeneca had only modest impact on the chemokine IL-8. Heat inactivation of serum did not decrease INFγ, IL-1β and TNFα concentrations in AstraZeneca vaccine-treated samples but had a strong inhibitory effect on IL-1β and TNFα release in Pfizer vaccine-treated samples, and also on IL-6 and IL-8 release in samples treated with either vaccine. The complement inhibitors offered limited or no effects.

The results show that COVID-19 vaccines can increase the release of various cytokines. The strong reduction of cytokine release after the inactivation of the complement and other serum components in comparison with a small effect of selective complement inhibitors suggests a complex role of the complement system in vaccine-induced cytokine release.

Prepared with the professional support of the Doctoral Student Scholarship Program of the Co-operative Doctoral Program of the Ministry of Innovation and Technology financed from the National Research, Development and Innovation fund.