Relationships between Serum IGF-1, IGFBP-2, Interleukin-1Beta and Interleukin-6 in Inflammatory Bowel Disease

Abstract

Aims: To study the relationships between serum IGF-1, IGFBP-3 and IGFBP-2 and interleukin (IL)-1β and IL-6 in inflammatory bowel disease (IBD). Methods: Thirty-seven patients (18 males, 19 females, aged 8.8–26.1 years) with IBD (Crohn’s disease, CD, n = 17, and ulcerative colitis, UC, n = 20) were studied. Patients were in relapse or remission according to established criteria. Serum IGF-1, IGFBP-3, IGFBP-2, IL-1β and IL-6 levels were determined in patients and 15 healthy controls (aged 8.2–19.0 years). Results: IGF-1 levels were lower in patients with CD in relapse compared with controls (p < 0.05). IGFBP-2 levels were higher in CD in relapse compared with other groups (all p < 0.05). In CD and UC patients (n = 37), IGF-1 levels were inversely correlated with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). IGFBP-2 levels correlated positively with ESR and IL-1β. IL-6 levels correlated positively with ESR and CRP. IL-1β levels were elevated in CD in relapse compared to controls (p < 0.05) and were higher in UC in relapse than in other groups (all p < 0.05). In combined CD/UC patients in relapse (n = 20), IL-1β levels were higher (p < 0.05) in patients with recto-sigmoiditis (n = 5) than in other patients. Conclusions: IGF-1, IGFBP-2 levels were related to IL levels, disease activity and anatomical distribution, consistent with active inflammation modifying the IGF-IGFBP system, possibly relevant to disturbance of growth.

Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis

“…Furthermore, the pattern was similar to that of TNFa. We previously described this increase in patients with inflammatory bowel diseases (21). These data suggest that IGFBP-2 on the one hand behaves as an acute phase protein, and on the other that the IGF/IGFBP system is modulated by some proinflammatory cytokines.…”

“…Equal aliquots of serum were subjected to electrophoresis on 12.5% acrylamide gels (27). The proteins were then transferred to nitrocellulose membranes and probed with specific antibodies against IGFBP-2 and -3 (Upstate Biotechnology , NY, USA; 1:2000) at 4 8C overnight as previously described (20,21). The bands were visualized by enhanced chemiluminescence as recommended by the manufacturer (Amersham Pharmacia Biotech, Little Chalfont, Bucks, UK).…”

“…We have previously shown in vitro that IL-1b and IL-6 modify IGFBP secretion into conditioned media (20), and in vivo, in inflammatory bowel diseases, that IGFBP-2 concentrations are increased together with IL-6, IL-1 and C-reactive protein (21).…”

Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the –174 IL-6 G/C polymorphism in children

“…Although growth-hormone expression is normal in Crohn's disease, reports (41) repeatedly have demonstrated a decreased IGF-I, with concomitant growth retardation. Because undernutrition depresses IGF-I, growth failure in children with Crohn's disease has been ascribed to poor nutrient intake (11,(42)(43)(44). However, our previous animal work showed that the inflammatory process depressed growth and IGF-I independently of nutrition (20).…”

Insulin-like growth factor system in remission and flare of inflammatory bowel diseases

“…Street et al, 28 who analyzed data from 37 patients with CD and UC, observed that the IGF -1 Significant interaction terms were discovered in the case of the IGF -1 marker. The mean values of the logarithm of IGF -1 in the nonactive CD group differed from those in the active CD group by 0.78-0.02 × age (P = 0.03) (FIGurE 1).…”