Genetic determinants of IL-6 expression levels do not influence bone loss in inflammatory bowel disease

Bone loss in inflammatory bowel disease (IBD) is presumed to be mediated by inflammation. Increased levels of the multifunctional cytokine IL-6 in inf lammatory diseases have been proposed to be the link in such "inflammation- mediated osteopenia." A recently described G/C polymorphism with an effect on transcription rate and plasma levels of IL-6 suggests a genetically dete rmined difference in the degree of the IL-6 response to stressful stimuli b etween individuals. This study aimed to assess the frequency of genotypes a nd haplotypes of the G/C polymorphism of IL-6 in IBD patients. A further ai m was to assess whether carriage of the potentially protective CC genotype is favorable with respect to the development of bone disease in IBD. The IL -6 polymorphism was typed in 105 IBD patients and 113 healthy controls. Bon e mineral density was evaluated at baseline and after a prospective 2-year- follow-up. The favorable CC genotype with decreased IL-6 release was not un derrepresented in IBD patients compared to healthy controls. Carriage of th is genotype was not protective with respect to the development of bone dise ase, either for the bone mineral density at baseline or for the prospective ly observed bone loss. Within the subgroup of patients who did not receive steroids during follow-up, the prospectively observed bone loss was even sl ightly higher in CC carriers, but differences did not reach significance. G enetically determined differences in the degree of the IL-6 response to str essful stimuli are no major predictors for the degree of bone disease in IB D patients.