Hyperactive immune cells (T cells) may be responsible for acute lung injury in influenza virus infections: A need for early immune-modulators for severe cases

Abstract

It has been believed that acute lung injury in influenza virus infections is caused by a virus-induced cytopathy; viruses that have multiplied in the upper respiratory tract spread to lung tissues along the lower respiratory tract. However, some experimental and clinical studies have suggested that the pathogenesis of acute lung injury in influenza virus infections is associated with excessive host response including a cell-mediated immune reaction. During the pandemic H1N1 2009 influenza A virus infections in Korea, we experienced a dramatic effect of immune-modulators (corticosteroids) on the patients with severe pneumonia who had significant respiratory distress at presentation and those who showed rapidly progressive pneumonia during oseltamivir treatment. We also found that the pneumonia patients treated with corticosteroids showed the lowest lymphocyte differential and that the severity of pneumonia was associated with the lymphocyte count at presentation. From our findings and previous experimental and clinical studies, we postulated that hyperactive immune cells (T cells) may be involved in the acute lung injury of influenza virus infections, using a hypothesis of 'protein homeostasis system'; the inducers of the cell-mediated immune response are initially produced at the primary immune sites by the innate immune system. These substances reach the lung cells, the main target organ, via the systemic circulation, and possibly the cells of other organs, including myocytes or central nerve system cells, leading to extrapulmonary symptoms (e.g., myalgia and rhabdomyolysis, and encephalopathy). To control these substances that may be possibly toxic to host cells, the adaptive immune reaction may be operated by immune cells, mainly lymphocytes. Hyperimmune reaction of immune cells produces higher levels of cytokines which may be associated with acute lung injury, and may be controlled by early use of immune-modulators. Early initiation and proper dosage of immune-modulators with antiviral agents for severe pneumonia patients may reduce morbidity and prevent progressive fatal pneumonia.

Acute Kidney Injury due to Rhabdomyolysis in H1N1 Influenza Infection

“…The authors speculated that all clinical features of influenza virus infection are caused by a virusinduced cytopathy. 5 In contrast to elevation of CPK levels in the course of H1N1 infection, only eight cases of rhabdomyolysis were reported since 2009 by Medline research. 1,[6][7][8][9][10][11][12][13] Three of these cases were reported from pediatric population and all cases of AKI were improved with supportive treatment.…”

Experimental study on anti-inflammatory activity of a TCM recipe consisting of the supercritical fluid CO2 extract of Chrysanthemum indicum, Patchouli Oil and Zedoary Turmeric Oil in vivo

“…Nevertheless, the excessive acute inflammation can be lethal (Zhou and Jiang, 2006). For example, after virus infection, the viral pneumonia (Lovato-Salas et al, 2010;Lee et al, 2011;Li et al, 2011), sequent bacterial pneumonia (Lee et al, 2010;Crystal et al, 2011), sequent encephalitis (Klopfleisch et al, 2007;Chen et al, 2010), and sequent angiocardiopathy (Mamas et al, 2008;Charlotte et al, 2009) were always the principal cause of the death. Hence, to protect the life quality of patients from the infection and its subsequent inflammatory complication, especially the acute inflammation, weights as much as irritant exclusion.…”

Alteraciones morfológicas en pulmón por la influenza A H1N1/v09 en autopsias, Colombia, 2009

“…Micrografía electrónica de tejido pulmonar con infección por virus de influenza A H1N1/v09. los casos graves y progresivos (20,21). Nicholson, et al (2003), concuerdan con que el balance entre la replicación viral y la respuesta inmunitaria del huésped determina el resultado de la infección y el daño en el tejido pulmonar; por ejemplo, las cepas de influenza muy virulentas, como la H5N1, poseen la capacidad de resistir los efectos antivirales de las citocinas del huésped (22) y, a su vez, inducen una expresión alta de citocinas asociada a la proliferación de macrófagos.…”