Association of IL-10 polymorphism with severity of illness in community acquired pneumonia.
BACKGROUND
The influence of genetic polymorphisms of interleukin (IL)-10, tumour necrosis factor (TNF)-alpha, and IL-6 gene promoters on severity of systemic inflammatory response syndrome (SIRS) associated with community acquired pneumonia (CAP) was studied.


METHODS
Using PCR-RFLP analysis we analysed a -1082G/A single nucleotide polymorphism (SNP) of the anti-inflammatory IL-10 gene, a -308G/A SNP of the pro-inflammatory TNF-alpha gene and a -174G/C SNP of the IL-6 gene. Illness severity was stratified according to SIRS score, calculated by presence of up to four physiological indices: temperature, white blood cell count, heart rate and respiratory rate (non-SIRS, SIRS 2, SIRS 3, and SIRS 4).


RESULTS
A statistically significant stepwise increase in frequency of the IL-10 G allele, associated with higher expression of the gene, was observed in patients with increasing severity of illness from non-SIRS (n=19) to SIRS 2 (n=17), SIRS 3 (n=33) and SIRS 4 (n=24). This was primarily due to a higher frequency of the GG genotype with increasing severity from non-SIRS through to SIRS 4. IL-10 G allele frequency was also increased in patients who died as a result of CAP (n=11) compared with CAP survivors (n=82) (p=0.01). No association was seen between the TNF-alpha -308G/A and IL-6 -174G/C SNPs and disease. Additionally, no interaction between all three SNP genotypes and disease severity was observed.


CONCLUSIONS
A polymorphism affecting IL-10 expression may influence the severity of illness in patients with CAP.
Gallagher
P M
PM
Division of Respiratory Research, Department of Medicine, RCSI Education and Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
Lowe
G
G
Fitzgerald
T
T
Bella
A
A
Greene
C M
CM
McElvaney
N G
NG
O'Neill
S J
SJ
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D017714:Community-Acquired Infections / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D011014:Pneumonia / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications; D012907:Smoking / Q000009:adverse effects; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10