Diagnostic value of cytokines in severe childhood Mycoplasma pneumoniae pneumonia combined with Adenovirus infection

In China, MP usually leads to the highest incidence of atypical pathogen pneumonia.ADV is a highly contagious pathogen, and the inflammatory response triggered by its pathogenesis can exacerbate the damage caused by the body’s infection and lead to further deterioration of the disease, which is a serious threat to children’s health [10]. MP is a pathogen that can be detected by directly competing with or scavenging other bacteria [11, 12]. Viral infections can damage the pulmonary epithelium and suppress the immune response, promoting bacterial growth and leading to secondary bacterial infections [13]. Several studies have shown [14,15,16]that the rate of positive ADV tests is significantly greater in hospitalized children and that the disease tends to be more severe when MP is co-infected with ADV. The severity of disease in patients with pneumonia depends on two aspects, i.e., immune resistance and tissue repair ability [17]. The common clinical symptoms in children with SMPP are pleural effusion, lung solidity, pulmonary atelectasis, respiratory distress, and even complications such as other organ injuries, infections, and hypoxic death.The present study showed that the number of days of hospitalization and duration of fever in the A1 and B1 groups were significantly greater than those in the A2 and B2 groups. Similarly, the duration of hospitalization was longer in severely ill patients, and the number of patients with pleural effusion or pulmonary solid lesions was also greater than that in the mild group. Additionally, there were significant differences in the immune response and whether severe disease developed in children with MPP with or without ADV infection, and although current clinical biomarkers are beneficial for the diagnosis of CAP, many indicators are still difficult to distinguish between bacterial and viral infections or between mild and severe infections.

With in-depth research on severe pneumonia in recent years, the use of serological indicators for this disease has improved continuously.CRP is an acute time-phase reactive protein, which rises sharply when the body is subjected to external stimuli, and the reaction is particularly acute during the acute onset of the disease [18].PCT, a serum procalcitonin prepeptide substance, has a significant increase in serum concentration during bacterial infection, and during viral infection, the body releases gamma- interferon, on the other hand, exhibits an inhibitory effect on the release of calcitoninogen [19].D-dimer is able to suggest abnormalities secondary to fibrinolytic activity, and the activation of the coagulation system in children with severe pneumonia can have a direct impact on the diffusion function of the respiratory membranes and on alveolar gas exchange function [20].In this study, the values of D-dimer, PCT, CRP, blood sedimentation, and LDH concentration in the severe patients were significantly higher than those in the mild group; in a related study [21], it was also clearly proposed that there was a direct relationship between the levels of calcitoninogen, CRP, D-dimer, and IL-6 concentration in the children with SMPP and the incidence of severe disease, which is in agreement with this study. In addition, the present study showed that WBC, N% and L% are not significant in suggesting viral infection, but N% and L% were significantly elevated in children with severe MP combined with ADV infection. PCT and LDH were significantly elevated in combination with ADV infection, suggesting that PCT and LDH can be used as indicators of an abnormal state in organisms when they are subjected to external stimuli.

Cytokines are mainly synthesized and secreted by intrinsic and adaptive immune cells in the body as a class of molecular peptides or glycoproteins with multiple active functions. IL-6, whose main role is to regulate and promote the immune response, is the cytokine that is initially expressed by the intrinsic nervous system in response to injury and can be markedly increased if the body is subjected to an external stimulus. The overexpression of IL-10 inhibits the clearance of pathogens, thus leading to secondary bacterial lung infections [22]. IL-17a levels have been found to correlate with disease severity in related studies [23]. MIKACENIC et al. [24]showed that IL-17a levels were strongly associated with increased percentages of neutrophils and that elevated IL-17a levels correlated with increased SOFA scores. According to related studies [21], IL-6, IL-8, and IFN-γ are significantly elevated in ADV infection [12, 25], and IL-1α, IL-2, IL-4, IL-5, IL-6, IL-8, IL-17 A, IFN-γ, and TNF-α are significantly elevated in MP infection [12, 26,27,28]. Because MPP combined with ADV can exacerbate the condition of children with pneumonia, it is necessary to explore meaningful cytokines to improve diagnostic accuracy during this stage of research. The results of this study showed that the expression levels of IL-6, IL-8, IL-10, IL-4, IL-12P70, and IFN-γ were greater in patients with combined ADV infection, which have a certain diagnostic value. These results show that the immune system disorders occur in children with Mycoplasma pneumoniae pneumonia complicated with Adenovirus infection, which leads to increased cytokine expression levels, suggesting that the development of severe disease is more likely. Therefore, we suggest that more active treatment measures should be taken for these children in the early stage. Several studies have shown that the expression of cytokines in patients with pneumonia is pathogen specific and that the host immune system is activated by the cellular immune response during viral infection [29, 30]. This finding is consistent with the present study. The expression levels of IL-6, IL-8, IL-10, and IL-17a were significantly greater in patients with severe disease, which have a certain predictive effect on disease severity. Therefore, targeted therapy for the above cytokines has an important role in improving prognosis and treatment. Studies have shown [31] that preventing interleukin synthesis and antagonizing the biological activity of interleukin have a certain effect on the treatment of asthma and respiratory tract infectious diseases. Whether these drugs can be used in the treatment of severe pneumonia in the future needs further research.

In this study, ROC curve analysis of the comparisons between groups A1 and A2 showed that among the individual indicators of N%, LDH, PCT, CRP and D-dimer, the diagnostic value of PCT was greater than that of PCT when it was greater than 0.33 (ng/ml); the diagnostic significance of the simultaneous elevation of the five indicators was greater than that of the individual indicators; the diagnostic value of the elevated concentrations of IL-6, IL-8, IL-10 and IL-17a was greater; and the diagnostic value of the elevated concentrations of the four cytokines was greater than that of the individual indicators. IL-10 has greater diagnostic value than the other cytokines, and a concentration greater than 16.02 (pg/ml) suggests severe disease; elevated concentrations of these four cytokines have significantly greater significance in the diagnosis of severe disease than do the individual indicators. The ROC curve suggested that the combination of the above indicators could play a synergistic role in the diagnosis of severe MP pneumonia in children, and the diagnostic effect was ideal.

In addition, this study is a retrospective analysis with a small sample size, which has certain limitations, and the specific pathways affected by various cytokines during the course of MPP still need to be further explored. This study only studied the cytokine changes in Mycoplasma pneumoniae with Adenovirus infection, and we will also study the changes in other viral infections in the future.

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