Increases in inflammatory and CD14^dim/CD16^pos/CD45^pos patrolling monocytes in sepsis: correlation with final outcome

Evidence on the changes in the absolute counts of monocyte subpopulations in sepsis is missing.

Firstly, absolute counts of circulating CD14^pos/HLA-DR^pos/CD45^pos monocytes were measured by flow cytometry in 70 patients with Gram-negative sepsis and in 10 healthy volunteers. In the second phase, immunophenotyping was performed and the absolute count of circulating inflammatory monocytes and of circulating CD14^dim/CD16^pos/CD45^pos patrolling monocytes were measured in another 55 patients and 10 healthy volunteers. Measurements were repeated on days 3, 7, and 10. Results were correlated with survival after 28 days.

Greater numbers of CD14^pos/HLA-DR^pos/CD45^pos monocytes were found on day 1 in survivors compared to nonsurvivors (p = 0.030). Receiver operating characteristic (ROC) analysis showed that a cutoff higher than 337 cells/mm³ on day 1 could discriminate between survivors and nonsurvivors with a positive predictive value (PPV) of 91.1%. Logistic regression including Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE) II score showed that an absolute count greater than 337 cells/mm³ was independently associated with unfavorable outcome (odds ratio (OR) 0.19, p = 0.050). The absolute counts of inflammatory and of CD14^dim/CD16^pos/CD45^pos monocytes were greater in patients than healthy controls during the entire 10 days of follow-up. The absolute counts on day 3 of CD14^dim/CD16^pos/CD45^pos monocytes were greater in survivors than nonsurvivors (p = 0.027). ROC analysis revealed that the cutoff at 27 cells/mm³ could discriminate between survivors and nonsurvivors with PPV of 94.1%. Logistic regression including age, SOFA score, and APACHE II score showed that an absolute count greater than 27 cells/mm³ was independently associated with unfavorable outcome (OR 0.06, p = 0.033). Logistic regression analysis showed that intra-abdominal infection on day 1 was predictive of low CD14^dim/ CD16^pos/CD45^pos count on day 3.

Circulating counts of inflammatory and patrolling monocytes are greatly increased in Gram-negative sepsis. Absolute counts of CD14^pos/HLA-DR^pos/CD45^pos monocytes on day 1 and CD14^dim/CD16^pos/CD45^pos monocytes on day 3 are independently associated with final outcome.

ClinicalTrials.gov, NCT01223690 . Registered retrospectively on 18 October 2010.