Interleukin-10 polymorphism in position -1082 and acute respiratory distress syndrome

Abstract

The GG genotype of the interleukin (IL)-10 promoter polymorphism in position -1082 (-1082GG) has been associated with increased IL-10 production. The current authors hypothesised that the -1082GG genotype is associated with the development of, and outcomes in, acute respiratory distress syndrome (ARDS). A nested case-control study was conducted in 211 Caucasian cases of ARDS and 429 controls who were admitted to an intensive care unit with sepsis, trauma, aspiration or massive transfusions. Cases were followed for organ failure and 60-day mortality. The -1082GG genotype was associated with the development of ARDS, but only in the presence of a significant interaction between the -1082GG genotype and age. Among patients with ARDS, the -1082GG genotype was associated with decreased severity of illness on admission, lower daily organ dysfunction scores and lower 60-day mortality. In conclusion, the high interleukin-10-producing -1082GG genotype may be associated with variable odds for acute respiratory distress syndrome development depending on age. Among those with acute respiratory distress syndrome, the -1082GG genotype is associated with lower mortality and organ failure. Further studies are needed to confirm these findings.

FIGURE 1

Flow diagram of study design and patient selection for the case-control study. ICU: intensive care unit; ARDS: acute respiratory distress syndrome.

FIGURE 2

Acute Physiology, Age and Chronic Health Evaluation (APACHE) III score on admission to the intensive care unit by genotype for the interleukin (IL)-10 -1082GA polymorphism among a) 640 cases and controls (AA: n=200; GA: n=292; GG: n=148; p=0.8) and b) the 211 ARDS cases (AA: n=58; GA: n=102; GG: n=51; p=0.008). The box denotes the interquartile range (25-75%) and the horizontal line indicates the median. Error bars `indicate the 95% confidence intervals. •: mean.

FIGURE 3

Odds ratio (OR) for the development of acute respiratory distress syndrome (ARDS) among individuals homozygous for -1082G allele (1082GG) compared with carriers of the -1082A allele after stratifying by age quartiles. OR were adjusted for direct pulmonary injury, septic shock, trauma, female sex, haematological failure (platelet <80,000·mm^-1), transfusion of red cells and Acute Physiology, Age and Chronic Health Evaluation III (without the arterial oxygen tension/inspiratory oxygen fraction component). There was significant interaction by age on the association between the interleukin-10 -1082GG genotype and development of ARDS (p<0.001). ^#: n=161; ^¶: n=165; ⁺: n=155; ^§: n=154.

FIGURE 4

Daily Brussels multiple organ dysfunction score for 28 days after development of acute respiratory distress syndrome (ARDS) according to interleukin-10 -1082GA genotype (···) for the 211 ARDS cases. In comparison with the -1082A carriers (-1082AA (—) and -1082GA (- - -)), ARDS patients with the -1082GG genotype had less organ failure over the course of their ARDS (p=0.03).

FIGURE 5

Kaplan-Meier 60-day survival curves in acute respiratory distress syndrome (ARDS) according to the interleukin-10 -1082GA genotype. Compared with -1082AA (—) and -1082GA (···) genotypes. ARDS patients with the -1082GG genotype (- - -) had better survival (p=0.004). •: censored.