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Inflammatory marker IL-6 indicates disease severity, predicts treatment failure in ulcerative colitis
Children with severe ulcerative colitis are less likely to respond to treatment with elevated levels of inflammatory cytokine interleukin-6, according to recent results.
In an ancillary study to the prospective, multicenter OSCI study, researchers evaluated levels of 12 inflammatory cytokines in serum samples collected from 79 children with acute severe ulcerative colitis (ASC). All patients received intravenous corticosteroids (IVCS), and samples were collected on the third day of treatment.
Second-line therapy was needed for 29% of the cohort who were nonresponsive to IVCS. Patients who responded had lower levels of interleukin-6 (IL-6) than those who did not (P=.003 in univariate analysis). Researchers noted a 40% increase in risk for IVCS failure for every 1 pg/mL of IL-6 increase (OR=1.4; 95% CI, 1.1-2.0). No significant differences were observed between patients who did and did not respond to treatment in the levels of other evaluated cytokines.
Multivariate analysis adjusting for duration of disease revealed a significant association between IL-6 levels and treatment response (OR=1.5; 95% CI, 1.1-2.0), with no association between response and duration (OR=1.02; 95% CI, 0.996-1.04). Adjusting for Pediatric Ulcerative Colitis Activity Index (PUCAI), however, eliminated the association with IL-6 (P=.32), with the significance assumed by PUCAI (P<.001), suggesting that the cytokine is a surrogate marker for ASC severity.
“Our observation that IL-6 is associated with corticosteroid failure could shed some light on potential mechanisms of steroid resistance,” the researchers wrote. “However, the association of IL-6 with corticosteroids failure is linked by multivariate analysis to disease severity, as measured by PUCAI. Although this suggests that IL-6 may only serve as a marker of severity, it also points to a specific role for this cytokine in mediating refractory disease course.”
Disclosure: See the study for a full list of relevant disclosures.