Immunological features in patients with pneumonitis due to influenza A H1N1 infection

Pneumonitis induced by pandemic influenza A H1N1 has a potential to cause respiratory failure, which is a risk factor for death. The underlying immunopathological mechanisms, however, have not yet been fully elucidated.

We investigated changes in plasma cytokines, T cell subsets, and C-reactive protein (CRP) in 16 hospitalized patients with pneumonia caused by 2009 H1N1 influenza infection. The patients were classified into a severe disease group and a mild disease group according to PaO2.

Cytokine profiles showed no changes in interferon gamma (IFN-gamma), interleukin 6 (IL-6), IL-8, or transforming necrosis factor alpha (TNF-alpha) levels throughout the observation period. Transforming growth factor beta (TGF-beta1) was overproduced in the severe group but not in the mild group. Accordingly, we also found some signs of pulmonary fibrosis during the recovery period. Elevated CRP levels and lymphopenia were common in both the severe and the mild group. After treatment, there was a significant elevation in lymphocytes in both groups, but a significant decrease in CRP in the mild group. Lymphocyte counts and CRP levels rapidly recovered to normal levels in all survivors posttreatment; otherwise it seemed to be related to poor prognosis.

Serial measurements of cytokines showed that only TGF-beta1 was overproduced, possibly in relation to the early use of corticosteroids, which may have downregulated immune responses to H1N1 infection. Pretreatment TGF-beta1 plasma concentrations and absolute lymphocyte counts were independent predictors of severity. However, the role of elevated TGF-beta1 in H1N1 infection-associated pulmonary fibrosis requires further investigation.