Age predicts cytokine kinetics and innate immune cell activation following intranasal delivery of IFNγ and GM-CSF in a mouse model of RSV infection

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and is further associated with increased healthcare utilization and cost of care in the first years of life. Severe RSV disease during infancy has also been linked to the later development of allergic asthma, yet there remains no licensed RSV vaccine or treatment. Pre-clinical and clinical studies have shown that disease severity and development of allergic asthma are associated with differences in cytokine production. As a result, stimulation of the innate host immune response with immune potentiators is gaining attention for their prospective application in populations with limited immune responses to antigenic stimuli or against pathogens for which vaccines do not exist. Specifically, macrophage-activating cytokines such as interferon gamma (IFNγ) and granulocyte colony-stimulating factor (GM-CSF) are commercially available immune potentiators used to prevent infections in patients with chronic granulomatous disease and febrile neutropenia, respectively. Moreover, an increasing number of reports describe the protective function of IFNγ and GM-CSF as vaccine adjuvants. Although a positive correlation between cytokine production and age has previously been reported, little is known about age-dependent cytokine metabolism or immune activating responses in infant compared to adult lungs. Here we use a non-compartmental pharmacokinetic model in naïve and RSV-infected infant and adult BALB/c mice to determine the effect of age on IFNγ and GM-CSF elimination and innate cell activation following intranasal delivery.

Pulmonary Susceptibility of Neonates to Respiratory Syncytial Virus Infection: A Problem of Innate Immunity?

“…Furthermore, it has been demonstrated that IFN γ production during neonatal infection influences the outcome of RSV pathology upon adult reinfection [ 109 ]. Indeed, it has been shown that intranasal injection of recombinant IFN γ in neonatal RSV-infected mice induces a better AM activation characterized by the expression of CAM markers (CD86 + , MHC II + and CCR7 + , and mannose receptor − ) on neonatal AMs and reduced viral load in the lungs [ 90 , 95 , 110 ].…”

Comparison of Immune Checkpoint Inhibitors between Older and Younger Patients with Advanced or Metastatic Lung Cancer: A Systematic Review and Meta-Analysis

“…In xenograft, mouse models have verified that age is connected with changes in immune system [11, 12]. When compared with younger ones, older mice further proved modificative cytokine kinetics [13] and reduced CD8 + T cell proliferation [14], and this is also associated with the decrement in T cell function [15] and CD28 expression [16, 17], which is a co-stimulatory signal for T cell activation [18]. But in clinical trials, Elias et al [19] reviewed efficacy and safety of ICI in patients with non-small cell lung cancer, melanoma, and renal cancer and found that there were no obvious age-associated difference in overall survival (OS) and side effects among those older and younger patients.…”

Data describing IFNγ-mediated viral clearance in an adult mouse model of respiratory syncytial virus (RSV)

“… The data presented here are related to the research article entitled “Age predicts cytokine kinetics and innate immune cell activation following intranasal delivery of IFNγ and GM-CSF in a mouse model of RSV infection” (Eichinger et al, 2017) [1] . The cited manuscript demonstrated that the macrophage-stimulating cytokine, interferon gamma (IFNγ), but not granulocyte macrophage-colony stimulating factor (GM-CSF), effectively enhanced viral clearance in infant mice infected with respiratory syncytial virus (RSV) following intranasal delivery.…”