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Open Access Research article

Serum activin A and B, and follistatin in critically ill patients with influenza A(H1N1) infection

Rita Linko1, Mark P Hedger2, Ville Pettilä1, Esko Ruokonen3, Tero Ala-Kokko4, Helen Ludlow5 and David M de Kretser2*

Author Affiliations

1 Intensive Care Unit, Department of Anaesthesia and Intensive Care Medicine, Division of Surgery, Helsinki University Hospital, Helsinki, Finland

2 Monash Institute of Medical Research, Monash University, Melbourne, Australia

3 Intensive Care Unit, Kuopio University Hospital, Kuopio, Finland

4 Departmentof Anaesthesiology, Division of Intensive Care, Oulu University Hospital, Oulu, Finland

5 Oxford Brookes University, Oxford, UK

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BMC Infectious Diseases 2014, 14:253  doi:10.1186/1471-2334-14-253

Published: 10 May 2014

Abstract

Background

Activin A and its binding protein follistatin (FS) are increased in inflammatory disorders and sepsis. Overexpression of activin A in the lung causes similar histopathological changes as acute respiratory distress syndrome (ARDS). ARDS and severe respiratory failure are complications of influenza A(H1N1) infection. Interleukin 6 (IL-6), which in experimental studies increases after activin A release, is known to be related to the severity of H1N1 infection. Our aim was to evaluate the levels of activin A, activin B, FS, IL-6 and IL-10 and their association with the severity of respiratory failure in critically ill H1N1 patients.

Methods

A substudy of a prospective, observational cohort of H1N1 patients in Finnish intensive care units (ICU). Clinical information was recorded during ICU treatment, and serum activin A, activin B, FS, IL-6 and IL-10 were measured at admission to ICU and on days 2 and 7.

Results

Blood samples from 29 patients were analysed. At the time of admission to intensive care unit, elevated serum levels above the normal range for respective age group and sex were observed in 44% for activin A, 57% for activin B, and 39% for FS. In 13 of the 29 patients, serial samples at all time points were available and in these the highest activin A, activin B and FS were above the normal range in 85%, 100% and 46% of the patients, respectively. No difference in baseline or highest activin A or activin B was found in patients with or without acute lung injury (ALI) or ARDS (P > 0.05 for all). Peak levels of IL-6 were significantly elevated in ALI/ARDS patients. Peak activin A and activin A/FS were associated with ventilatory support free-days, severity of acute illness and length of ICU stay (P < 0.05 for all).

Conclusions

Higher than normal values of these proteins were common in patients with H1N1 infection but we found no association with the severity of their respiratory failure.

Keywords:
Activin A; Activin B; Follistatin; H1N1 influenza; Acute respiratory distress syndrome; Interleukin 6