Evaluation of Fc-receptor positive (FcR+) and negative (FcR-) monocyte subsets in sepsis.

The monocyte/macrophage (Mphi is central in the regulation of the immune response in states of trauma and sepsis. Because monocyte subsets, characterized by expression of the Fc-receptor (FcR), were shown to play distinct immunologic roles in trauma, it was the objective of this study to assess insights into the functional role of FcR positive (FcR+) and negative (FcR-) subclasses in surgical sepsis. In a prospective study, peripheral blood Mphi from 20 septic patients and 10 healthy volunteers were evaluated on consecutive days after the onset of sepsis. FcR+/- subsets were separated by rosetting with antibody-coated human erythrocytes. Receptor expression and synthesis of proinflammatory cytokines were used to evaluate the functional role of these cells. We demonstrated a significant monocytosis (350%; p<.01) and suppression of human lymphocyte antigen (HLA-DR) expression (35%; p<.05). Synthesis of Interleukin-1beta (IL-1beta; e.g., Day 1: 230+/-30 pg/mL) and Interleukin-6 (IL-6; e.g., Day 1: 1920+/-350 U/mL) were significantly higher (p<.05) in FcR+ subsets than in controls (IL-1beta: 100+/-5 pg/mL; IL-6: 353+/-75 U/mL). Tumor necrosis factor-alpha (TNF-alpha) was elevated in FcR+ monocytes but did not reach a significant value. Interleukin-8 (IL-8) synthesis showed only on Day 1 and in controls significant differences in FcR+ and FcR- cells (Day1: FcR-: 19.6+/-4.1 nM; FcR+: 9+/-4.3 nM). Sepsis results in a significant shift toward FcR+ monocytes. This cell population is characterized by high proinflammatory cytokine synthesis. The extent of this shift seems to identify a group of high risk septic patients that might benefit from immunomodulatory therapy.

Functional analysis of monocyte subsets in surgical sepsis.

BACKGROUND: Sepsis still remains a major cause of death after surgery. Impaired monocyte (Mphi) function and disruption of monocyte (Mphi/T-cell interaction were shown to be crucial for the development of septic complications in these patients. It was the objective of the study to assess more insights in Mphi behavior in surgical sepsis by means of analysis of Fc receptor- and human leukocyte antigen DR (HLA-DR) expression in Mphi subsets, and to evaluate the kinetics of these changes. METHODS: In a prospective study, 20 septic patients and 10 healthy control subjects were included. Peripheral Mphi were isolated on consecutive days after onset of sepsis, and FcR positive (FcR+) and negative (FcR-) subsets were separated by rosetting with antibody-coated human erythrocytes. Cell surface receptor expression and in vitro cytokine production were used to determine the clinical importance of these subsets. RESULTS: A significant monocytosis (3.5-fold; p < 0.01) and suppression of HLA-DR receptor expression (35%, p < 0.01) which correlate with sepsis severity and outcome could be demonstrated. There was a significant increase of FcR+ subsets in sepsis compared with control subjects (60% vs. 24%; p < 0.05). In vitro stimulation of Mphi subsets and peripheral blood mononuclear cells revealed suppressed interferon-gamma synthesis (p < 0.05 up to 0.01) from day 1 to day 5, elevated neopterin release (p < 0.05) on day 14 and increased synthesis rates of proinflammatory cytokines (e.g., interleukin-1beta); p < 0.05) predominantly in FcR+ subsets. CONCLUSIONS: Sepsis results in a significant monocytosis and suppression of HLA-DR receptor expression, which are correlating with sepsis severity and outcome. A significant shift toward FcR+ Mphi subsets can be found. This subpopulation resembles the previously described "angry macrophage" that is characterized by high proinflammatory cytokine synthesis and suppressed antigen presentation and that contributes to a disruption of adequate Mphi/T-cell interaction, rendering the host anergic toward opportunistic infections. The extend of HLA-DR suppression and the shift toward FcR+ Mphi might characterize a high risk patient subpopulation, which could benefit from immunomodulatory strategies.

A novel method for measuring saccade profiles using the scanning laser ophthalmoscope.

Most existing techniques for accurately measuring angular eye position vs time during a saccade (the saccade profile) need either contact to the eye or are restricted in time resolution. In this paper we introduce a new noninvasive method, with high spatial and temporal resolution, for determining saccade profiles using a scanning laser ophthalmoscope (SLO). This method uses the fact that images of a moving object taken with the SLO are not blurred (as are images from video cameras) but show a tilt with respect to images of the same stationary object. A mathematical framework is given that allows determination of a saccade profile from a restricted number of consecutive SLO video fields of the fundus during a saccade. The angular resolution obtained by this method is below 0.1 deg, and the maximum time resolution near 1 msec. Measured saccade profiles could be well approximated by a gamma function, the first derivative of which yields the saccade velocity profile. Measurements of peak saccade velocity as a function of saccade amplitudes (main sequence) using our method show good agreement with results obtained by other authors.