Background: Elevated
interleukin-6 (IL-6) and complement activation are associated with detrimental effects of
inflammation in
coronary artery disease (CAD). The
complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the
IL-6 receptor (IL-6R)-antagonist
tocilizumab on the expression of the
anaphylatoxin receptors in whole blood from
non-ST-elevation myocardial infarction (
NSTEMI) patients. Separately,
anaphylatoxin receptor expression in peripheral blood mononuclear cells (PBMC) from patients with different entities of CAD was investigated. Materials and Methods:
NSTEMI patients were randomized to one dose of
tocilizumab (n = 28) or placebo (n = 32) and observed for 6 months. Whole blood samples drawn at inclusion, at day 2, 3 and after 6 months were used for
mRNA isolation. Plasma was prepared for analysis of complement activation measured as sC5b-9 by ELISA. Furthermore, patients with different CAD entities comprising
stable angina pectoris (SAP, n = 22), non-ST-elevation
acute coronary syndrome (NSTE-ACS, n = 21) and
ST-elevation myocardial infarction (
STEMI, n = 20) were included. PBMC was isolated from blood samples obtained at admission to hospital and
mRNA isolated.
Anaphylatoxin-receptor-expression was analyzed with qPCR using
mRNA from whole blood and PBMC, respectively. Results: Our main findings were (i)
Tocilizumab decreased C5aR1 and C5aR2
mRNA expression significantly (p < 0.001) and substantially (>50%) at day 2 and 3, whereas C3aR expression was unaffected. (ii)
Tocilizumab did not affect complement activation. (iii) In analyzes of different CAD entities, C5aR1 expression was significantly increased in all CAD subgroups compared to controls with the highest level in the
STEMI patients (p < 0.001). For C5aR2 and C3aR the expression compared to controls were more moderate with increased expression of C5aR2 in the
STEMI group (p < 0.05) and C3aR in the NSTE-ACS group (p < 0.05). Conclusion: Expression of C5aR1 and C5aR2 in whole blood was significantly attenuated by IL-6R-inhibition in
NSTEMI patients. These receptors were significantly upregulated in PBMC CAD patients with particularly high levels of C5aR1 in
STEMI patients.