Transforming Growth Factor-β, Macrophage Colony-Stimulating Factor and C-Reactive Protein Levels Correlate with CD14highCD16+ Monocyte Induction and Activation in Trauma Patients

Abstract

Severe injury remains a leading cause of death and morbidity in patients under 40, with the number of annual trauma-related deaths approaching 160,000 in the United States. Patients who survive the initial trauma and post-traumatic resuscitation are at risk for immune dysregulation, which contributes to late mortality and accounts for approximately 20% of deaths after traumatic injury. This post-traumatic immunosuppressed state has been attributed to over-expression of anti-inflammatory mediators in an effort to restore host homeostasis. We measured a panel of monocyte markers and cytokines in 50 severely injured trauma patients for 3 days following admission. We made the novel observation that the subpopulation of monocytes expressing high levels of CD14 and CD16 was expanded in the majority of patients. These cells also expressed CD163 consistent with differentiation into alternatively activated macrophages with potential regulatory or wound-healing activity. We examined factors in trauma plasma that may contribute to the generation and activation of these cells. The percentage of CD14highCD16+ monocytes after trauma correlated strongly with plasma C-reactive protein (CRP) transforming growth factor-β (TGF-β), and macrophage colony-stimulating factor (M-CSF) levels. We demonstrate a role for TGF-β and M-CSF, but not CRP in generating these cells using monocytes from healthy volunteers incubated with plasma from trauma patients. CD16 is a receptor for CRP and IgG, and we showed that monocytes differentiated to the CD14highCD16+ phenotype produced anti-inflammatory cytokines in response to acute phase concentrations of CRP. The role of these cells in immunosuppression following trauma is an area of ongoing investigation.

Differential expression of monocyte/macrophage markers between active and inactive stage of patients with Behçet's disease

“…CD32 also plays an essential role in the removal of antigen-antibody complexes from the circulation and cell-tocell interactions mediating antibody-dependent cell-mediated cytotoxicity. CD14 + CD16 + monocytes are reportedly increased in sepsis patients with severe infection [40] and efficiently produce the pro-inflammatory cytokine TNF-α, while they produce no or little of the anti-inflammatory cytokine IL-10 [41]. Our results also showed significantly up-regulated frequencies of CD14 + CD16 + subsets in BD patients (Figure 3) and markedly elevated IL-10 levels in improved inactive BD patients compared to active BD patients (Figure 6).…”

Pentraxins: Structure, Function, and Role in Inflammation

“…Monocytes and macrophages are key initiators and regulators of innate immune responses following trauma. In a study of 50 trauma patients, we observed an increase in an activated monocyte/macrophage population (CD14 high CD16 + CD163 + ) in the blood that was highly correlated with CRP levels, as well as M-CSF and TGF- β [239], M-CSF and TGF- β found in trauma plasma could induce this phenotype in normal monocytes. Although it was not essential for inducing the phenotype, CRP activated M-CSF differentiated monocytes to produce anti-inflammatory cytokines, IL-10 and IL-1RA.…”

Monocyte Subsets and Inflammatory Cytokines in Acute Decompensated Heart Failure

“…Similar studies in obesity and trauma demonstrate that monocyte subsets have prognostic value with regards to disease severity and clinical outcomes 26, 27 . Importantly, in all of these diseases, our current understanding has progressed first from an appreciation that absolute monocyte levels are predictive, to a more nuanced appreciation that monocyte heterogeneity and ultimately the functional consequences of this heterogeneity contribute to disease pathogenesis.…”