In the present prospective study we interrogated miRNA expression in a set of sepsis patients and found, by performing genome-wide profiling by microarray in leukocytes followed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on plasma samples that miR-150 is significantly down regulated in respect with healthy controls levels and can be used for assessing the severity of the sepsis.
This study is novel in several aspects. First, it addresses a significant medical condition, the sepsis, from a new perspective—the involvement of small non-coding RNAs. Sepsis is the major cause of death among critically ill patients in ICU. Total mortality for patients with acute postoperative sepsis is about 30%–35%; however, the mortality rate for patients with severe sepsis is over 50% 
. Consequently, severe sepsis is a disease in the need for critical care resources. We found that in sepsis patients the microRNoma (defined as the full spectrum of expressed miRNAs) is different from that in healthy controls, both in leukocytes (considered the cells involved in the immune disturbances characteristic of sepsis) and plasma on the first day of admission to the ICU. We found by microarray or qRT-PCR that the levels of three miRNAs — miR-150
, and miR-342-5p
— are at least twice as dysregulated in leukocytes from patients than in those from healthy controls. Supporting these findings is a recent in vitro
profile of the human leukocyte miRNA response to endotoxemia in which leukocyte RNA was isolated from venous blood samples obtained from three healthy male volunteers before and 4 h after LPS infusion and profiled for miRNA expression 
. Five miRNAs consistently responded to LPS infusion, four of which were downregulated (miR-146b
, and let-7g
) and one of which was upregulated (miR-143
. Also, miR-150
was found to control c-Myb expression in vivo
in a dose-dependent manner over a narrow range of miRNA and c-Myb concentrations, and this dramatically affected lymphocyte development and response 
. These data further strengthen the functional significance of miR-150
downregulation in sepsis patients. Furthermore, abnormal processing of miR-21
transcript was recently reported in ICU patients suffering from sepsis-induced multiple organ failure 
, expanding the spectrum of miRNA alterations in sepsis.
Second, the recent identification of miRNAs in serum and plasma from healthy individuals and individuals with pathologic conditions, such as cancer, opens up the possibility of exploring miRNAs as biomarkers of disease 
. To our knowledge, this is the first report of miRNA measurement in plasma from sepsis patients. We found not only that miR-150
levels are significantly different in patients and healthy controls, but also that the levels of miR-150
correlate with SOFA scores (but not with WBC). SOFA is a scoring system used to track a patient's status while in the ICU; it is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems 
. We identified a ratio between the quantitative RT-PCR expression of miR-150
and a nonvariable control miR-192
that can be used to assess the severity of sepsis based on its correlation with the SOFA score. Additional candidates for large studies could be miR-182
that we found differentially expressed in sepsis versus control leukocytes.
Finally, we revealed a new potential pathogenetic mechanism explaining some of the immune system dysfunctions in sepsis patients. The malfunction of regulatory mechanisms during sepsis can result in a loss of control of inflammation, eventually leading to profound immunosuppression and host damage 
. Our study points to a miRNA regulation of pro- and anti-inflammatory genes involved in sepsis. We found that the expression levels of miR-150
correlated with those of main immune response genes, such as TNF-alpha, IL-10, and IL-18. Furthermore, the putative spectrum of targets of miR-150
is highly enriched in genes involved in immune system functions. Therefore, in addition to miR-155 
and miR-125 
could be one of the main regulatory miRNAs of immune function, and our study unraveled the clinical significance of the miR-150
expression correlation with cytokine expression in patients with sepsis.
In conclusion, although the functions of most human miRNAs have yet to be discovered, miRNAs have emerged as key regulators of gene expression. The present data support the hypothesis that miRNAs are main regulators of the immune system, and abnormal expression has been found and can be used as a diagnostic and prognostic marker in immune disease. Sepsis is the newest addition to the long list of disease states proved by studies in patients to be linked to abnormal miRNA expression. One of the important regulators is miR-150, and this is significantly abnormally expressed in both leukocytes and plasma from sepsis patients. Our study is the first to identify a specific miRNA profile and to interrogate about the clinical significance of miRNA variations in sepsis patients. Due to the limited number of cases originating in the same center and to the bias toward intra-abdominal causes of sepsis, larger multi-institutional studies with higher numbers of patients will establish the final prognostic significance of our initial findings.