C-Reactive Protein Mediating Immunopathological Lesions: A Potential Treatment Option for Severe Influenza A Diseases

Abstract

Severe influenza diseases with high mortality have been frequently reported, especially in those patients infected with avian influenza A (H5N1, H7N9 or H10N8) or during a pandemic. Respiratory distress, which is attributed to alveolar damage associated with immunopathological lesions, is the most common cause of death. There is a wealth of information on pathogenesis or treatment options. In this study, we showed that high levels of C-reactive protein (CRP) were induced and correlated with complement activation in patients infected with severe influenza A (H5N1, H7N9 or H10N8), and higher levels were induced in fatal patients than in survivors. CRP treatment enhanced the phagocytosis of monocytes THP-1 to H5N1 virus as well as the expression of proinflammatory cytokines or apoptosis-associated genes in THP-1 cells or pneumocytes A-549 respectively. CRP may link to proinflammatory mediators contributing to activation of complement and boosting inflammatory response in severe influenza infections. Compound 1,6-bis(phosphocholine)-hexane improved the severity and mortality of mice infected with lethal influenza virus significantly. These observations showed that CRP is involved in deterioration of severe influenza diseases, and indicated a substantial candidate molecule for immunotherapy of severe influenza diseases.

A Comparative Study on the Clinical Features of Coronavirus 2019 (COVID-19) Pneumonia With Other Pneumonias

“…Previous studies suggested that excessive immune response played an important role on pathogenesis of severe influenza or SARS [24]. And IL-6 and CRP may link to the excessive immune response [25,26]. In this study, our results also showed abnormally increased CRP and IL-6 in most of both NCOVID-19 and NON-NCOVID-19 patients.…”

C-reactive protein as a biomarker of severe H1N1 influenza

“…In animal and cell culture models, among other cytokines, over-synthesis of interleukins (such as IL-1β and IL-6) and TNF-α were shown to play a major role in the development of a wide range of severe disease outcomes [reviewed in 8, 11]. Furthermore, cytokine storm has been implicated previously both in severe H5N1 and H7N9 influenza [26, 27] where excessive immune activation, particularly the complement activation mediated by CRP, was reported [27]. …”

“…CRP is an acute phase reactant activated by cytokines to trigger the complement component of the immune system [10, 11, 27]. Previous studies in influenza A have shown that overactivation of the complement cascade contributes to the cytokine storm and can play a role in the pathogenesis of, rather than protection against, influenza [26, 27].…”

<p>Nomogram for the Individualized Prediction of Survival Among Patients with H7N9 Infection</p>

“…We also find that the peak CRP level may be considered a particularly important factor when evaluating the probability associated with survival in H7N9 cases. According to a study conducted by Gao and colleagues, 31 CRP is involved in the deterioration observed in severe influenza infection and may be a candidate molecule for immunotherapy treatment. A previous study 31 indicated that CRP treatment can improve the prognosis of patients with H7N9 VI.…”