Background: Glucocorticoids (GCs) are steroid hormones used to induce remission in moderate-to-severe inflammatory bowel disease (IBD). A substantial fraction of patients do not respond to GC treatment and require alternate therapies or surgery. At present, nonresponse can only be assessed empirically by observing continued disease activity. Aim: To identify biomarkers of GC response in IBD patients and provide insights into the biological processes underlying variation in clinical response to GCs. Methods: 18 GC-responsive and 18 GC-nonresponsive IBD patients were retrospectively recruited from our IBD Center. This sample included 14 patients with ulcerative colitis (UC) and 22 patients with Crohn's disease (CD), all previously treated with oral or intravenous steroids. In peripheral blood mononuclear cells from each patient, we performed in vitro assays to measure GC inhibition of three different immune stimulants (phytohemagglutinin [PHA], α-CD3/α-CD28, and lipopolysaccharide [LPS]) controlling for age, gender, ethnicity, and current medications. Results: In both diseases, we found that inhibition of PHA-mediated T cell proliferation was significantly associated with clinical response (P=0.04). Inhibition of proliferation due to direct T cell receptor stimulation using α-CD3/α-CD28 was also significantly associated with clinical response in UC patients (P=0.009) (Figure 1), but not in CD patients (P=0.78). Interestingly, inhibition of LPS-mediated cytokine secretion showed the strongest association with clinical response across both diseases (P=0.005) (Figure 2). Conclusions: Extending on previously observed associations between inhibition of PHA and α-CD3/α-CD28-mediated proliferation and clinical response, we show that inhibition of LPS stimulation shows an even stronger association with clinical response to GCs in patients with IBD. These results are consistent with the importance of bacterial recognition and innate immunity in the etiology of IBD. This assay could be a powerful predictor of clinical response and future studies are needed in order to replicate these observations.