Cytokine imbalance in infants receiving extracorporeal membrane oxygenation for respiratory failure.
BACKGROUND
It is likely that the imbalance between the pro- and anti-inflammatory cytokines will determine the outcome in infants with severe respiratory failure receiving extracorporeal membrane oxygenation (ECMO).


OBJECTIVE
We determined if there was an imbalance between pro- and anti-inflammatory cytokines in serial bronchoalveolar lavage (BAL) fluid obtained from survivors and non-survivors of ECMO.


METHODS
We therefore measured the cellular changes and the molar ratios of pro-inflammatory and anti-inflammatory cytokines in serial BAL fluid obtained from survivors and non-survivors of ECMO. Fifteen infants surviving ECMO (median age 1 day, range 1-120) and 7 who did not (28 days, range 1-402) were studied.


RESULTS
In the lungs of survivors, the increased proportion of airway neutrophils at presentation decreased with time and was matched by a parallel increase in percent alveolar macrophages as the infants' condition improved. The pro- and anti-inflammatory pulmonary cytokine ratios were static in the survivors. In the non-survivors, the ratio of tumour necrosis factor-alpha (TNF-alpha) against soluble TNF-receptor 1 (sTNF-R1) and soluble TNF receptor 2 (sTNF-R2) was increased at days 2-3 when compared to the survivors, but the molar ratio interleukin-1beta (IL-1beta)/soluble IL-1 receptor antagonist (sIL-1RA) was largely undetectable due to undetectable IL-1beta.


CONCLUSIONS
These data suggest that the infants who survive ECMO resolve their pulmonary inflammation and that in non-survivors the ratio of TNF-alpha against its receptor antagonists is increased and is associated with a poor outcome. Furthermore, this group of infants were unable to produce significant concentrations of IL-1beta.
Mildner
Reinout J
RJ
Heartlink ECMO Centre, Glenfield Hospital, Leicester, UK.
Taub
Nicholas
N
Vyas
Julian R
JR
Killer
Hillary M
HM
Firmin
Richard K
RK
Field
David J
DJ
Kotecha
Sailesh
S
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis*; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D009504:Neutrophils; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000032:analysis; D012131:Respiratory Insufficiency / Q000378:metabolism / Q000628:therapy*; D012795:Sialoglycoproteins / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha