Serum soluble triggering receptor on myeloid cells-1 (sTREM-1) is elevated in systemic lupus erythematosus but does not distinguish between lupus alone and concurrent infection.

We sought to determine serum triggering receptor expressed on myeloid cell-1 (sTREM-1) level in a cohort of patients with systemic lupus erythematosus (SLE). Serum sTREM-1 level of 98 patients with SLE and 49 healthy controls was assayed by ELISA. Serum sTREM-1 level was significantly elevated in a cohort of 78 unselected consecutively recruited patients with SLE (mean 1.1 ± 2.8 ρg/ml, median 0.02 ρg/ml) compared to that of the controls (mean 0.11 ± 0.3 ρg/ml, median 0 ρg/ml; p < 0.0001). We also determined serum sTREM-1 level of 20 SLE patients with a concurrent infection (mean 0.6 ± 1.1 ρg/ml, median 0.12 ρg/ml) and found it not statistically significant compared with that of the patients without infection. Serum sTREM-1 level did not correlate with SLE disease activity. Our finding of elevated serum sTREM-1 level suggests an increased shedding of TREM-1 in SLE and a possible novel pathway of innate immune response in autoimmunity.

The tight calorie control study (TICACOS): a prospective, randomized, controlled pilot study of nutritional support in critically ill patients.

PURPOSE: To determine whether nutritional support guided by repeated measurements of resting energy requirements improves the outcome of critically ill patients. METHODS: This was a prospective, randomized, single-center, pilot clinical trial conducted in an adult general intensive care (ICU) unit. The study population comprised mechanically ventilated patients (n = 130) expected to stay in ICU more than 3 days. Patients were randomized to receive enteral nutrition (EN) with an energy target determined either (1) by repeated indirect calorimetry measurements (study group, n = 56), or (2) according to 25 kcal/kg/day (control group, n = 56). EN was supplemented with parenteral nutrition when required. RESULTS: The primary outcome was hospital mortality. Measured pre-study resting energy expenditure (REE) was similar in both groups (1,976 ± 468 vs. 1,838 ± 468 kcal, p = 0.6). Patients in the study group had a higher mean energy (2,086 ± 460 vs. 1,480 ± 356 kcal/day, p = 0.01) and protein intake (76 ± 16 vs. 53 ± 16 g/day, p = 0.01). There was a trend towards an improved hospital mortality in the intention to treat group (21/65 patients, 32.3% vs. 31/65 patients, 47.7%, p = 0.058) whereas length of ventilation (16.1 ± 14.7 vs. 10.5 ± 8.3 days, p = 0.03) and ICU stay (17.2 ± 14.6 vs. 11.7 ± 8.4, p = 0.04) were increased. CONCLUSIONS: In this single-center pilot study a bundle comprising actively supervised nutritional intervention and providing near target energy requirements based on repeated energy measurements was achievable in a general ICU and may be associated with lower hospital mortality.

Inhaled aerosolized insulin: a "topical" anti-inflammatory treatment for acute lung injury and respiratory distress syndrome?

Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are forms of pulmonary edema that result from robust local and systemic inflammatory states, such as sepsis. The morbidity and mortality associated with ALI and ARDS are significant and the treatment of these conditions presents a formidable challenge. Controlling hyperglycemia with insulin is a core component of patient management in the critically ill. Insulin treatment also exerts beneficial metabolic effects beyond glucose control, as well as non-metabolic effects, in insulin-resistant states. For instance, insulin inhibits NF-kappaB--dependent synthesis of pro-inflammatory factors and attenuates production of ROS. Indeed, intravenous administration of insulin ameliorates pulmonary injury and dysfunction in the LPS model of ALI. Most recently, an inhalable insulin formulation was shown to effectively reduce glucose concentrations with minimal impact on long-term pulmonary function. We propose that administering inhalable insulin to hyperglycemic ALI/ARDS patients could directly reduce alveolar inflammation while reducing circulating glucose levels.

Signal transducer and activator of transcription-1 (STAT1), but not STAT5b, regulates IGF-I receptor gene expression in an osteosarcoma cell line.

The IGF-I receptor (IGF-IR) exhibits potent mitogenic, antiapoptotic, and transforming activities. Previous studies have suggested that the expression of the IGF-IR gene is negatively regulated by certain cytokines, including interferon-gamma (IFN-gamma). The potential involvement of STAT proteins in transcriptional regulation of the IGF-IR gene by IFN-gamma was addressed by transient coexpression of vectors encoding STAT1 and STAT5b, together with an IGF-IR promoter luciferase reporter, in the osteosarcoma-derived cell line Saos-2. Physical interactions between IFN-gamma-induced transcription factors and the IGF-IR promoter region were examined by electrophoretic mobility shift assays (EMSA). The results obtained indicate that the mechanism of action of IFN-gamma involves stimulation of STAT1 which, in turn, binds IFN-gamma activation sites (GAS) in the IGF-IR regulatory region, thus suppressing promoter activity. Taken together, our results suggest that the IGF-IR gene is a novel target for STAT1 action and that at least part of the inhibitory effects of STAT1 may involve repression of the strongly antiapoptotic IGF-IR gene.