Involvement of interleukin-4 and -10 in inflammatory bowel disease

Abstract

The pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD) may be associated with a decreased production of cytokines suppressing macrophage and T-cell functions: interleukins (IL) -4 and IL-10. Serum concentrations of IL-4 and IL-10 were measured using an ELISA technique, and intestinal IL-4 and IL-10 mRNA was detected by a reverse transcriptase polymerase chain reaction (RT-PCR) in 34 patients with inflammatory bowel disease (IBD) (20 with UC and 14 with CD) and compared to 12 control subjects. The superoxide production was measured spectrophotometrically in activated PMNs initially incubated in the presence of IL-4 or IL-10. No differences were found in numbers of cells that might be potential IL-4 or IL-10 producers (T cells, macrophages, B cells, and mast cells) in biopsy specimens using immuno- and histochemistry. IL-4 mRNA was detectable in specimens from 77.8% of the UC patients (P > 0.05) and 0% of the CD patients (P < 0.05), as compared to 81.8 in controls, and was significantly different (P < 0.0001) between UC and CD patients. The IL-10 amplification product was detectable in specimens from 30.0% UC patients (P < 0.003), but not in CD patients (78.6%, P > 0.05) as compared to controls (91.7%). The circulating protein levels of IL-4 were below the detection limit in all groups (detection limit 4 pg/ml), while the median IL-10 concentration was 12.5 pg/ml in UC, 18.1 pg/ml in CD, and 19.5 pg/ml among controls (detection limit 3 pg/ml), which did not differ in any of the three groups (P > 0.05). Finally, the superoxide production was inhibited and delayed by the addition of IL-10 (P < 0.01), whereas IL-4 only delayed this parameter. In conclusion, apart from the well-known suppressive effect on proinflammatory cytokine production, IL-4 delays and IL-10 inhibits superoxide generation. IL-4 mRNA expression is decreased in intestinal tissue from CD patients, while IL-10 mRNA expression is decreased in majority of UC patients, suggesting different immunopathogenesis of the two diseases.

Impaired anti-inflammatory efficacy of n-butyrate in patients with IBD

“…These observations are in agreement with previous studies [44,45]. It has also been reported that patients with IBD produce lower amounts of IL-10 [46,47]. Our findings of a decreased IL-1b induction in patients with IBD are in line with a recent study showing a failure of acute inflammation in CD patients due to the presence of diminished concentrations of inflammatory markers like IL-8 and IL-1b [48].…”

The natural plant product sophocarpine ameliorates dextran sodium sulfate-induced colitis in mice by regulating cytokine balance

“…The reverse anti-inflammatory action is provided by IL-4 and IL-10. IL-4 is able to block antibody-dependent cytotoxicity as well as to suppress the spontaneous and induced production of IL-1β, TNF-α, PGE 2, IL-6, IL-8, and nitric oxide [18].…”

Anti-inflammatory Cytokines and Cytokine Antagonists

“…In partial support of this concept, a decrease in the expression of IL-4 mRNA has been detected in the intestinal tissue recovered from patients with Crohn's disease, but not ulcerative colitis [121]. In an attempt to enhance expression of IL-4 systemically, the murine IL-4 transgene was expressed by adenoviral gene therapy in a rat model of colonic immune activation and inflammation (trinitrobenzene sulfonic acid-induced colitis) [122].…”