Why interleukin-10 supplementation does not work in Crohn’s disease patients

Table 1 Summary of key findings from interleukin-10 trials in human and animal studies

Ref.	Model	Intervention	Outcome
	Human
Colombel et al[22]	65 patients having recently undergone intestinal resection surgery	4 μg/kg daily or 8 μg/kg twice weekly for 12 wk	No clear evidence of effect
Fedorak et al[23]	95 mild to moderately active CD (CDAI 200-350)	1, 5, 10 or 20 μg/kg of daily for 4, 20 wk follow up	Improved clinical response (based on CDAI score) and improved endoscopic appearance
Schreiber et al[26]	329 therapy-refractory chronic active CD (CDAI 200-400)	1, 4, 8 or 20 μg/kg of Tenovil subcutaneously for 28 d	Non-significant clinical improvements
van Deventer et al[28]	46 patients with active steroid-resistant CD (CDAI 200-350)	0.5, 1, 5, 10 or 25 μg/kg daily for 1, 3 wk follow up	Reduction in the average score of CDAI
Braat et al[128]	10 patients with moderate to severe CD	10 enteric-coated capsules containing 1010 cfu of LL-Thy12 twice daily for 7 d	Clinical benefit observed in 8 of 10 patients, including 5 showing complete remission
	Animal
Barbara et al[121]	DNB induced colitis Spf Sprague-Dawley rats	Ad5IL-10 (5 × 108-1 × 1010 pfu)	Improved colitis macroscopically and histologically and decreased MPO activity and LTB4 levels
Grool et al[123]	40 male NZ white rabbits formalin-immune complex induced colitis	100 or 500 μg/kg single IV infusion of rIL-10	Anti-inflammatory response as measured by decreased mucosal damage, leukocyte recruitment, MPO and LTB4
Ribbons et al[124]	TNBS induced colitis in 74 Sprague-Dawley rats	0.5, 5, 50, 500 μg/kg rIL-10 subcutaneous injection twice daily for 5 d	Mild anti-inflammatory effects Significant reduction in MPO
Sasaki et al[125]	3% DSS induced C57B6 mice	Intra-peritoneal administration of adIL-10	Significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon
Tomoyose et al[126]	4% DSS induced colitis BALB/c mice	Recombinant mouse rIL-10 (1, 100, 1000 unit/mL)	Marked improvement in intestinal inflammation Inhibition of tissue damage and production of pro-inflammatory cytokines
Steidler et al[127]	DSS induced and spontaneous IL10-/- mouse models of colitis	Daily intragastric inocula of 2 × 107 or 109 LL-mIL10	Reduced histological score by 50% in DSS and prevented onset of colitis in IL-10-/- mice

CD: Crohn’s disease; CDAI: Crohn’s disease activity index; cfu: Colony forming units; MPO: Myeloperoxidase; LTB4: Leukotriene B4; TNBS: 2, 4, 6 trinitrobenzenesulfonic acid; DSS: Dextran sodium sulphate; adIL-10: Adenoviral IL-10; DNB: Dinitrobenzene sulphonic acid; Spf: Specific pathogen free; Ad5IL-10: Human type 5 adenovirus + murine IL-10; pfu: Plaque forming units; LL-mIL10: Lactococcus lactis secreting murine IL-10.