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. 1997 Nov;41(5):651–657. doi: 10.1136/gut.41.5.651

Imbalance of the interleukin 1 system in colonic mucosa—association with intestinal inflammation and interleukin 1 receptor agonist genotype 2

T Andus 1, R Daig 1, D Vogl 1, E Aschenbrenner 1, G Lock 1, S Hollerbach 1, M Kollinger 1, J Scholmerich 1, V Gross 1
PMCID: PMC1891562  PMID: 9414973

Abstract

Background—Interleukin 1 (IL-1) α and β are potent cytokines which play key roles in inflammation. They are controlled by IL-1 receptor antagonist (IL-1ra). 
Aims—To investigate the influence of mucosal inflammation and IL-1ra genotype on the IL-1ra:IL-1 balance. 
Patients and methods—IL-1α, IL-1β, and IL-1ra were measured by enzyme linked immunosorbent assay (ELISA) in biopsy specimens taken from inflamed and non-inflamed colon of 60 patients with Crohn's disease (CD), 34 with ulcerative colitis (UC), 15 inflammatory controls, and 103 non-inflamed controls. IL-1ra genotype was determined by polymerase chain reaction and gel electrophoresis. 
Results—IL-1α and IL-1β were significantly increased in inflamed mucosa in inflammatory bowel disease (IBD) (CD: 53.5 (22.4) and 409.9 (118.7) pg/mg protein, respectively; UC: 18.9 (6.8) and 214.5 (78.2) pg/mg, respectively) and non-IBD patients (19.2(7.4) and 281.4 (121.0) pg/mg, respectively; p<0.0001) compared with normal controls (2.8 (0.6) and 30.6 (5.6) pg/mg, respectively). In CD IL-1α and β were also significantly increased in non-inflamed mucosa (6.1 (1.3) pg/mg and 88.7 (17.4) pg/mg, respectively; p<0.0012). IL-1ra:(IL-1α+β) ratios were significantly decreased in inflamed mucosa of patients with CD (182 (45); p<0.0001), UC (425 (136); p=0.0018) and without IBD (221 (76); p<0.0001), and in non-inflamed mucosa in CD (369 (149); p<0.0001) compared with normal controls (1307 (245); p<0.0001). Patients with IL-1ra genotype 2 had slightly but significantly reduced mucosal IL-1ra concentrations (p=0.003). The greatest difference was seen in colonic biopsy specimens from patients with inflamed Crohn's disease. 
Conclusion—Mucosal inflammation can modulate the balance of the IL-1:IL-1ra system in colonic mucosa. 



Keywords: interleukin 1; interleukin 1 receptor antagonist; inflammatory bowel disease; Crohn's disease; mucosal inflammation; genotype

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Figure 1 .

Figure 1

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: Different IL-1ra genotypes. The following genotypes are shown (from left to right) 1/3, 2/2, 1/1, 1/2, 1/2. A λ Pst l digest was used as size standard. 


Figure 2 .

Figure 2

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: IL-1α (A), IL-1β (B), IL-1ra (C), and IL-1ra:IL-1α+β ratios (D) in colonic mucosa. Data were logarithmically transformed (to achieve a normal distribution) and were expressed as means (95% confidence intervals). Asterisks indicate statistically significant differences compared with non-inflamed controls. 


Figure 3 .

Figure 3

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: Intraindividual concentrations of IL-1α (A), IL-1β (B), IL-1ra (C), and IL-1ra:IL-1α+β ratios (D) in inflamed and non-inflamed colonic mucosa of patients with CD. Data were logarithmically transformed (to achieve a normal distribution) and were expressed as means (95% confidence intervals). Asterisks indicate statistically significant differences between inflamed and non-inflamed regions. 


Figure 4 .

Figure 4

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: IL-1ra in colonic mucosa and genetic polymorphism of IL-1ra. Data were logarithmically transformed (to obtain a normal distribution) and are expressed as mean (SEM). 


Figure 5 .

Figure 5

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: Genetic polymorphism of IL-1ra and mucosal concentrations of IL-1α, IL-1β, and IL-1ra. IL-1(α+β) (A), and IL-1ra (B) were determined and ratios of IL-1ra:IL-1α+β were calculated (C). In order to combine the data of different groups the influence of diagnosis and inflammation was excluded by Z normalisation. The Z normalised values of the data are given as mean (95% confidence interval) and grouped by the number of IL-1ra genotype 2 alleles. The asterisk indicates a statistically significant difference compared with the patients with no IL-1ra allele. 


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