Editorial from Guest Editor [Hot topic: Novel Inflammatory Biomarkers in Diseases (Guest Editor: Yu Chen)]

Inflammation, as defined by Stedman's concise medical dictionary, is “a fundamental, stereotyped complex of cytologic and chemical reactions that occur in affected blood vessels and adjacent tissues in response to an injury or abnormal stimulation caused by a physical, chemical, or biologic agent” [1]. It is well established that inflammatory response is a feature and pathophysiological mechanism of many diseases including infectious diseases, cardiovascular diseases (CVDs), acute kidney injury (AKI), inflammatory bowel diseases, allergy, asthma and respiratory distress syndrome, etc. Recently, inflammatory factors have been emerging as novel biomarkers for the prediction, diagnosis, screening, and monitoring for various diseases. Many of these inflammatory biomarkers are not just by standers, but actually involve the underneath pathogenesis and play a fundamental role in the development of diseases. This theme topic issue of the Inflammation Allergy - Drug Targets focuses on recent advances on emerging inflammatory biomarkers. Distinguished authors including clinical biochemists, physicians and research scientists in the field were invited to review and summarize several important inflammatory biomarkers for their clinical utility on disease diagnosis and management, and their roles on pathophysiology of diseases. Potential therapies targeting these inflammatory biomarkers were also incorporated in their discussions. Current evidence suggest that high sensitivity C-reactive protein (hsCRP) is an independent CVD risk factor and the measurement of hs-CRP is being recommended in men older than 50 years and women older than 60 years of age who are at intermediate risk (10% to 19%) according to their Framingham risk scores and who do not otherwise qualify for lipid-lowering therapy (i.e., if their LDL-C is less than 3.5 mmol/L) [2]. hsCRP of less than 2 mg/L is also recommended as a secondary (optional) therapeutic target (once low-density lipoprotein cholesterol is at goal) [2]. Maekawa et al. review major relevant findings associates with the clinical implications of CRP and pentraxin3 (PTX3), which belong to the pentraxins superfamily involving in innate immunity, and their role in CVD [3]. Their discussion indicates that in addition to the significance as a prognostic arm, PTX3 might be cardio- and atheroprotective through the modification of innate immunity and inflammatory response; however, whether CRP function contributes to CVD remains unclear. Compared with many other inflammatory biomarkers, plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) has demonstrated a high specificity for vascular inflammation because of the origin source of this enzyme mainly from inflammatory cells in atherosclerotic plaques and its association with LDL, HDL and VLDL. Interestingly, Lp-PLA2 may play as a cardio-protective if associated with HDL, whereas Lp-PLA2 may be pro-athergenic, pro-inflammatory, and pro-apoptotic if the enzyme bound to apolipoprotein-B-containing lipoproteins. Ahmed et al. provide an overview on biochemistry, biological function, and clinical utility as an independent CVD biomarker of Lp-PLA2 [4]. They are also in favor of the role of Lp-PLA2 as a potential pharmacologic therapeutic target for atherosclerosis. Heat shock proteins (Hsps) are highly conserved proteins that protect organisms against deleterious and noxious stimuli or subsequent injury. Heat shock proteins are well known for their primarily function as molecular chaperones which facilitate the folding and refolding, assembly and stabilization of other proteins. Recently, Hsps have indicated important regulatory roles in both innate and acquired immunity and inflammation [5]. Furthermore, Hsp27, Hsp60 and Hsp90 are all found releasing from cardiomyocytes into circulation after injury and as potential biomarkers for myocardial infraction or heart failure [6-8]. Jones et al. summarize the recent work from their group as well others on Hsps protection against myocardial ischemia and inflammation [9]. They also review their studies on insulin-induced myocardial protection and its realtionship with Hsps. It appears that Hsps protection on heart and inflammation may be time- and stimulus- dependent through different mechanisms. Once these fundamental processes are well understood, targeted therapeutic intervention may be possible. AKI, the previously so-called acute renal failure, is a common clinical situation with serious consequences in hospitalized patients. There is an urgent call for novel biomarkers for the early diagnosis of AKI to expedite appropriate interventions to prevent morbidity and mortality. The current clinically widely used serum creatinine and its derivative estimated glomerular filtration rate are far from ideal AKI markers in that serum creatinine is only valid for assessment for renal function once it reaches a steady state. Serum creatinine is not very useful for kidney injury for lacking of enough sensitivity and specificity and it is greatly affected by race, gender, age, muscle mass, hydration and protein intake [10]. Blood urea nitrogen, another biomarker incorporated into clinical practice several decades ago, is now considered as suboptimal for AKI as well. There is a systematic review by Huang and Don-Wauchope on the clinical utility of kidney injury molecule 1(Kim-1), a membrane protein on proximal tubule epithelium, in the prediction, diagnosis and prognosis of AKI [11]. They analyze eight clinical studies and conclude that Kim-1 is a potential urinary biomarker in the early detection of AKI within 24 hours after kidney insult. Neutrophil gelatinase-associated lipocalin (NGAL) is another potential early biomarker for AKI. Its application is just being started in clinical practice and there is a new urine NGAL assay available on automated ARCHITECT® immunoassay analyzer [12]. The clinical utilization of NGAL in AKI has already been reviewed in many excellent articles [13, 14]. Giasson et al. systematically review the clinical utilities of NGAL in body fluids (blood, urine, etc.) as a new biomarker for non-AKI diseases such as chronic kidney diseases (including lupus nephritis, glomerulonephritis, obstruction, renal dysplasia, polycystic kidney disease, and IgA nephropathy), vascular disorders (including ANCA-associated vaculitis, Kawasaki disease, coronary artery disease and stroke), cancer, preeclampsia, infection, allergy, etc. [15]. It seems that NGAL may be a promising biomarker for numerous non-AKI diseases, as well as for AKI. In conclusion, these inflammatory biomarkers discussed in this theme topic issue are shredding lights for the diagnosis, prediction, prevention, prognosis and monitoring of many diseases. With better understating of their roles in the pathophysiological mechanism of disease, potential therapeutic targets may also be developed. However, most of these biomarkers are pre-clinical or only at the early stage of clinical usage. More multi-center controlled prospective studies with rigorous study design and enough participants using standardized and validated analytical methods are needed to further evaluate their clinical utilities in diagnosis and therapy.