Plasma arachidonic acid-rich phospholipids in Crohn's disease: response to treatment.

1. Increased concentrations of plasma polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease. However, it is not known whether there are corresponding changes in circulating phospholipids--the major source of fatty acids in the plasma. 2. Fasting plasma samples were obtained from 17 control subjects and 13 patients with active Crohn's disease [Simple Index of Crohn's Disease Activity (SICDA) > 6] before, and 2 and 8 weeks after, treatment with either a peptide diet or oral prednisolone. 3. Before treatment, the Crohn's disease patients had mildly active disease (SICDA 9.9 +/- 0.8, erythrocyte sedimentation rate 26.4 +/- 6.5 mm/h, serum C-reactive protein 2.8 +/- 0.4 mg/l). The proportions of the polyunsaturated phosphatidylcholine species, 16:0-20:4 (10.0 +/- 0.7%) and 16:0-22:6 (7.1 +/- 0.8%), were both significantly higher than those in healthy controls (7.6 +/- 0.5%, P < 0.01 and 5.3 +/- 0.5%, P < 0.05 respectively). 4. After 2 weeks treatment, the SICDA in the Crohn's disease patients decreased to 3.2 +/- 0.6 (P < 0.0001 compared with the pretreatment value), and there were corresponding falls in the erythrocyte sedimentation rate (to 12.6 +/- 2.7 mm/h, P < 0.05) and C-reactive protein concentration (to 1.7 +/- 0.3 mg/l, P < 0.05)--these improvements being maintained at 8 weeks. There was also a fall to normal values in 16:0-20:4 (to 7.7 +/- 0.6%, P < 0.01 compared with the pretreatment value) and in 16:0-22:6 (to 5.7 +/- 0.5%, P not significant), by week 8. 5. The proportions of polyunsaturated phosphatidylcholine molecular species were increased in the plasma of patients with active Crohn's disease, but fell to normal levels during disease remission. These observations are consistent with the theory that, in active Crohn's disease, the mucosal phospholipids containing polyunsaturated fatty acids are increased, contribute to eicosanoid synthesis and 'spill' into the plasma.

The induction of specific proteases for insulin-like growth factor-binding proteins following major heart surgery.

Insulin-like growth factors (IGF-I and IGF-II) circulate bound to specific high-affinity binding proteins (IGFBPs). Recent evidence has shown that in pregnancy and severe illness, specific proteases modify these binding proteins, reducing their affinity for IGFs. We have studied 12 patients, undergoing elective coronary artery vein-bypass graft surgery, for the appearance of these proteases and have demonstrated the induction of two independent, heat-labile, cation-dependent proteases. Proteolytic activity directed against IGFBP-3 was detected in all patients between 24 h and 5 days after surgery; the second IGFBP-4 specific protease was active 1 h after sternotomy. The total IGF-I levels were found to decrease following surgery, with the IGF-I distribution in the plasma being radically altered from that seen prior to the operation. One day after the operation the majority of the IGF-I, instead of being bound in the relatively inert 150 kDa complex, was associated with the smaller binding proteins which are more readily accessible to the tissues. These findings are in contrast to pregnancy where, despite similar proteases, the majority of the IGF-I remains in the 150 kDa complex. The alteration seen in IGF-I distribution after surgery did not appear to be a direct result of the IGFBP-3 proteolytic activity or an effect of the addition of heparin to the circulation. The potential increase in bioavailability of IGFs caused by the alteration in carrier protein may play a pivotal role in countering the catabolic state induced by surgery.