This prospective cohort study was to explore the relationships between serum IL-2 levels and the severity and prognosis of CAP patients. The study's key findings included: (1) serum IL-2 increased gradually with different CAP severity scores; (2) there was a positive correlation observed between the CAP severity scores and the levels of serum IL-2; (3) the risk of unfavorable prognosis was increased with elevated serum IL-2 levels on admission in CAP patients; (4) the combination of serum IL-2 and CAP severity scores improved the prediction powers for severity and death.
In the human organism, IL-2 is predominantly released by activated T lymphocytes, while dendritic cells and macrophages also possess the capacity to secrete limited quantities of IL-2 [28]. The effects of IL-2 are contingent upon its dosage and affinity for receptors, leading to a diverse range of outcomes [29–32]. Published research studies have shown that IL-2 is strongly connected to a number of biological processes of many lung diseases. In an experimental model utilizing mice, IL-2 is significantly elevated and can exacerbate allergic asthma through the toll-like receptor 9-IL-2 axis [33]. Patients with COVID-19 who are undergoing cytokine storm demonstrate elevated serum levels of IL-2, which serves as an immunopathologic attribute [34–36]. In addition, IL-2 can synergistically promote vascular leakage with TNF-α in superantigen or pathogen-induced acute lung injury [20, 37]. However, the exact connection between IL-2 and CAP has not yet been identified. Therefore, IL-2 levels were examined in all CAP patients. Based on our study, we discovered that patients with CAP had gradually rising serum IL-2 levels as their severity scores rose. Furthermore, serum IL-2 levels on admission were strongly connected with CAP severity scores. Additionally, various forms of organ impairment were found in CAP patients [22–26]. Therefore, we estimated the relationships between serum IL-2 and various clinical parameters. The facts from our study revealed that serum IL-2 were positively correlated with WBCs, other inflammatory factors, and indices related to hepatic and renal functions, such as urea nitrogen, creatinine, AST, ALT. The implications of these findings propose that IL-2 could play a pivotal role in the pathophysiological mechanisms of CAP.
Numerous investigations have substantiated the findings that IL-2 is involved in the progression of many other diseases and is associated with its prognosis. High expression of IL-2 is positively correlated with the survival period of multiple myeloma patients [38]. The presence of IL-2 exacerbates the poor prognosis of colorectal cancer patients [39]. When IL-2 is elevated in patients diagnosed with non-Hodgkin lymphoma, their survival rates are diminished [40]. But the relationship between IL-2 and the prognosis was unclear in CAP patients. Consequently, the relationship between IL-2 and various prognosis were examined in CAP patients. Our research revealed that CAP patients who exhibited higher levels of IL-2 on admission had significantly increased risks of requiring mechanical ventilation, vasoactive medications, ICU admission, mortality, and prolonged hospital stay. The predictive abilities of serum IL-2, other inflammatory markers, and severity scores for severity and mortality were assessed through ROC curve. Compared to CAP severity scores, or inflammatory indicators, the combination of serum IL-2 and severity score greatly increased the prediction abilities of severity and death in CAP patients. Thus, the results from our study indicated that higher levels of serum IL-2 on admission were associated with an increased probability of unfavorable outcomes in CAP patients.
IL-2 is recognized to be a common pro-inflammatory factor that is widely expressed in human immune cells [28]. CAP can be caused by various pathogenic infections, mainly included gram-positive bacteria, gram-negative bacteria, viruses and other atypical pathogens. Gram-negative bacterial cell membranes contain LPS. When it binds to TLR4 expressed on airway epithelial cells [41], it activates the NF-κB transcription factor, causing pro-inflammatory cytokines like IL-2, IL-4, IL-5, and IL-6 to be released [42]. Additionally, SARS-CoV-2 infection can activate NF-κB, resulting in a "cytokine storm" that releases plenty of inflammatory factors, including IL-2, which in turn leads to lung damage in COVID-19 patients [43]. High IL-2 concentration can induce vascular leakage syndrome and cytokine storms, leading to interstitial pulmonary edema and multi-organ failure [44–46]. An animal experiment indicated that Streptococcus pneumonia infection incurs pulmonary inflammation and IL-2 elevation in the lungs [47]. Therefore, we speculate that pathogenic infection may activate NF-κB signaling and evoke inflammatory cytokines secretion, leading to IL-2 elevation in lungs. Then, IL-2 is secreted, and the levels of IL-2 are elevated in CAP patients.
This research endeavors to illuminate the role of IL-2 in CAP. It predominantly demonstrates a positive correlation between the levels of serum IL-2 concentration on admission and the severity as well as unfavorable prognosis of CAP patients. Nevertheless, the present investigation possesses certain limitations. First, future research necessitates larger sample sizes and the inclusion of multiple centers, as a result of the limited sample size at present. Furthermore, only serum samples were utilized to assess IL-2 levels. Further investigation is warranted to assess the levels of IL-2 in pulmonary tissues and bronchoalveolar lavage fluid. Lastly, the current study only was an epidemiological examination of the population. The mechanism underlying the enhancement in IL-2 remained unidentified in CAP patients. Animal experiments are required to perform and explore the exact mechanism.