Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

Clinical utility of insulin-like growth factor 1 and 2; determination by high resolution mass spectrometry.

Measurement of insulin-like growth factor-1 (IGF-I) has utility for the diagnosis and management of growth disorders, but inter-assay comparison of results has been complicated by a multitude of reference standards, antibodies, detection methods, and pre-analytical preparation strategies. We developed a quantitative LC-MS method for intact IGF-I, which has advantages in throughput and complexity when compared to mass spectrometric approaches that rely on stable isotope dilution analysis of tryptic peptides. Since the method makes use of full-scan data, the assay was easily extended to provide quantitative measurement of IGF-II using the same assay protocol. The validated LC-MS assay for IGF-I and IGF-II provides accurate results across the pediatric and adult reference range and is suitable for clinical use

Endogenous epoxygenases are modulators of monocyte/macrophage activity.

Arachidonic acid is metabolized through three major metabolic pathways, the cyclooxygenase, lipoxygenase and CYP450 enzyme systems. Unlike cyclooxygenase and lipoxygenases, the role of CYP450 epoxygenases in monocyte/macrophage-mediated responses is not known

Example extracted ion chromatograms (smoothed) for IGF-I (∼250 µg/L) and IGF-II (460 µg/L) from a patient sample and inset calibration curves for both analytes (A).

<p>Representative unsmoothed MS spectra from the extracted ion chromatograms for IGF-I (B) and IGF-II (C).</p

Spectra of modified IGF-I found in commercial QC pools and patient samples (5a, oxidized IGF-I in commercial QC pools, Δ m/z 2.2856 expected, Δ m/z 2.2854 observed; 5b, putative N-2 proteolytic fragment of IGF-I in a patient sample Δ m/z 22.0106 expected, Δ m/z 22.0111 observed).

<p>Spectra of modified IGF-I found in commercial QC pools and patient samples (5a, oxidized IGF-I in commercial QC pools, Δ m/z 2.2856 expected, Δ m/z 2.2854 observed; 5b, putative N-2 proteolytic fragment of IGF-I in a patient sample Δ m/z 22.0106 expected, Δ m/z 22.0111 observed).</p