Cytokine-related genotypic differences in peak interleukin-6 blood levels of patients with SIRS and septic complications.
BACKGROUND
The aim of the present study was to investigate whether tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6-related genotypic differences affect IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS) in an intensive care unit (ICU).


METHODS
Seven polymorphisms of TNF, IL-1, and IL-6-related polymorphisms were studied with an allele-specific polymerase chain reaction. One hundred and thirteen patients diagnosed with SIRS whose sequential organ failure assessment scores were > or =5 at the time when their daily measured IL-6 blood level peaked during the ICU stay (IL-6 max) were examined. IL-6 max, survival, and septic complications were compared between carriers and non-carriers of less frequent alleles, indicated as allele*2, in each polymorphism.


RESULTS
In single nucleotide polymorphism (SNP) at position -238 site of TNF-alpha (TNF-alpha-238*G/A), IL-6-596*G/A, and IL-6-174*C/T, allele*2 frequencies were much lower in the Japanese than in the Caucasian population. IL-6 max was significantly higher in allele*2 carriers of IL-1beta-511*C/T. Associations were found between susceptibility to septic shock and allele*2 carriage for both IL-1beta-511*C/T and TNF-alpha-308*G/A, and also between poor prognosis and allele*2 carriage in both IL-1 receptor antagonist second intron various number of tandem repeats polymorphism (IL-1raRN*1-5) and TNF-alpha-308*G/A. IL-1beta-511*C/T and IL-1raRN*1-5 were in linkage disequilibrium in this study population.


CONCLUSIONS
Carriers of less frequent alleles in IL-1-related polymorphisms appear to have significant vulnerability to production of excessive IL-6 blood levels and to deterioration in septic shock.
Watanabe
Eizo
E
Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba UniversityChiba City, Japan. eizo-watanabe@umin.ac.jp
Hirasawa
Hiroyuki
H
Oda
Shigeto
S
Shiga
Hidetoshi
H
Matsuda
Kenichi
K
Nakamura
Masataka
M
Abe
Ryuzo
R
Nakada
Takaaki
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis*; D015850:Interleukin-6 / Q000097:blood*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012772:Shock, Septic / Q000235:genetics; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000150:complications / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha