Introduction: Macrophages are the predominant cell capable of removing toxic hemoglobin at sites of tissue injury, and CD163 has been recognized as the hemoglobin scavenger receptor present on the macrophage cell surface. In this study, we explored the levels of soluble CD163 (sCD163) in patients with intracerebral hemorrhage (ICH) to ascertain whether sCD163 was associated with clinicoradiologic features and long-term functional outcomes.
Methods: Our ICH cohort was comprised of 50 patients with moderate-sized basal ganglia hematomas. We collected serial serum and cerebrospinal fluid (CSF) at pre-specified timepoints (24 hours, 48 hours, 3-5 days, 6-8 days, and greater than 10 days post-ictus). We also obtained samples from 10 healthy controls. Levels of sCD163 were measured by enzyme-linked immunosorbent assay. A linear mixed model was used to compare sCD163 values among various groups, using a Bonferroni correction for multiple test adjustment. The method of generalized estimating equations was used to determine associations with dichotomized outcomes (modified Rankin Scale score 0-3 versus 4-6).
Results: Compared to healthy controls, serum sCD163 was higher in the ICH patients (40.6 versus 128.4 ng/mL). Within the ICH cohort, early values (24 hours to 5 days post-ictus) of serum sCD163 were significantly higher in patients who elaborated minimal perihematomal edema (PHE) (200.3 in patients with less than 10 mL PHE versus 71.8; p = 0.046). 6 to greater than 10 days post-ictus, sCD163 levels tailed off for patients with less PHE whereas levels rose in patients with greater PHE. Continued subacute elevation of sCD163, particularly in the CSF, was highly associated with poorer outcomes, both at discharge and at 90 days (p < 0.001). These associations were independent of age, gender, peak hematoma volume, and ICH score; there was a statistically significant association of CSF sCD163 values with degree of intraventricular hemorrhage (p = 0.04).
Conclusions: sCD163 may be a dynamic marker in ICH, with acute levels distinguishing edema patterns and subacute levels predicting functional outcome. Further studies are needed to confirm these findings and explore the pathophysiology behind these observations.