Alteration in Serum Levels of Inflammatory Cytokines during Parainfluenza Virus Type 1 Infection in Patients with Severe Multiple Disabilities

Abstract

SUMMARY: An epidemic of parainfluenza virus type 1 (PIV1) infection occurred in a hospital ward housing patients with severe motor and intellectual disabilities. Twenty-three infected patients exhibited persistent high fever for 4-16 days and decreased lymphocyte counts. One-half of the symptomatic patients had increased blood monocyte counts and the other half progressed to bronchitis or pneumonia. We also compared levels of 27 cytokines in the sera of 21 patients during the acute and normal phases of infection. Cytokine levels were measured with a bead immunoassay performed using the Luminex Multiplex System. Serum levels of interleukin (IL)-1Ra, C-C-motif chemokine (CCL) 2, and C-X-C-motif chemokine (CXCL) 10 significantly increased during the acute phase. In contrast, the serum level of CXCL8 decreased slightly. These results suggest the involvement of monocytes/macrophages and respiratory epithelial cells in the initial stage of PIV1 infection. A previous report using nasal wash samples also found a significant increase in levels of CXCL10 during the acute phase. Hence, CXCL10 may be a useful marker of a cytokine storm produced upon viral infection. However, alterations in levels of IL-1Ra, CCL2, and other cytokines differed between the 2 studies, suggesting that the cytokine profile produced systemically at viral infection is different from that produced at mucosal sites. Further analysis is required to clarify the mechanisms underlying cytokine production during PIV1 infections.Human parainfluenza virus (PIV) is commonly identified as a causative agent of respiratory tract infections (1). Among the 4 types of PIV, types 1 (PIV1) and 3 belong to the genus Respirovirus, and types 2 and 4 belong to the genus Rubulavirus. Reportedly, PIV1 and 3 cause infections mainly in the lower respiratory tract, whereas PIV2 and 4 mainly infect the upper respiratory tract. In particular, PIV1 frequently infects epithelial cells of the respiratory tract and induces lower respiratory tract infections, such as bronchitis and pneumonia, especially in immunocompromised hosts, children, and the elderly (1,2).Severe viral infections are known to induce cytokine storms, which impact the progression of infectious diseases (3). During a cytokine storm, interferons (IFNs), interleukins (ILs), chemokines, colony-stimulating factors (CSFs), and tumor necrosis factors (TNFs) are produced in varying amounts, resulting in various immune responses. In addition, infections by the same virus have been reported to induce cytokine storms with different cytokine profiles (2,4). Therefore, specific cytokine responses to individual infectious disease remain under investigation.Here, we report an epidemic of PIV1 infection that occurred in a hospital ward housing patients with severe multiple disabilities. We analyzed the clinical characteristics of PIV1 infection and changes in serum levels of cytokines in symptomatic patients.In a 60-bed ward at Ehime Medical Center (Ehime, Japan), 23 patients (14 men and 9 women) aged 18-68 years (average age,...

Serum IFN-γ-induced protein 10 (IP-10) as a biomarker for severity of acute respiratory infection in healthy adults

“…ARIs caused by parainfluenza virus in adults with severe multiple disabilities had an almost 9 fold increase in the serum concentration of IP-10 during the acute phase of the infection [16]. Additionally, in other populations with underlying illnesses, such as asthma or COPD, IP-10 concentrations measured in serum [16,[32][33][34] or nasal [31] samples or IP-10 gene expression [19,35] again correlated with acute respiratory infections leading to exacerbations. Although IP-10 concentrations are higher in smokers with COPD but not in smokers generally [36], the number of smokers in our cohort is small and hence unlikely to influence IP-10 concentrations.…”

“…Other research groups have reported that nasal IP-10 is correlated with ARI, primarily among people with underlying illness [29][30][31]. ARIs caused by parainfluenza virus in adults with severe multiple disabilities had an almost 9 fold increase in the serum concentration of IP-10 during the acute phase of the infection [16]. Additionally, in other populations with underlying illnesses, such as asthma or COPD, IP-10 concentrations measured in serum [16,[32][33][34] or nasal [31] samples or IP-10 gene expression [19,35] again correlated with acute respiratory infections leading to exacerbations.…”

“…Although IP-10 is elevated with influenza infections compared to controls, IP-10 has not been shown to be useful for identifying severe influenza infections [37]. Although large increases in IP-10 concentrations were observed with parainfluenza infections, no correlations with clinical severity of infection were apparent [16]. In contrast, we found that IP-10 concentrations correlate with ARI symptoms on the day measured early in the course of the infection, as well as with severity and duration of ARI in a cohort of healthy individuals.…”

“…IP-10 production is associated with both protection from and facilitation of infection. Recent reports have indicated increased levels of IP-10 occur with acute respiratory infections (ARIs) and suggest a biomarker role for IP-10 [16][17][18][19].…”

Curtailing virus-induced inflammation in respiratory infections: emerging strategies for therapeutic interventions

“…In multiple animal models of respiratory diseases, the treatment with XC221GI led to controlling the levels of CXCL9, CXCL10, CXCL11, IL-6 and IL-8, and to decrease of extent of the pathogen-driven cytokine storm. Notably, while the properties of TNF-alpha, IL-6 and IL-8 as hyperinflammatory drivers are well known [Vardhana and Wolchok, 2020;Sinha et al, 2020], the ligands of chemokine receptor CXCR3 chemokine receptor ligands, namely, CXCL10 (IP-10), CXCL11 (I-TAC), and CXCL9 (MIG), are deserving more detailed attention (Landry and Foxman, 2018;Hayney et al, 2017;Van Raemdonck et al, 2015;Matsuda et al, 2014). These chemokines are produced by epithelial cells, monocytes, endothelial cells, and smooth muscle cells of the airways when stimulated by IFNγ, type I interferons, and tumor necrosis factor TNFα.…”