The anti-inflammatory effects of circulating fatty acids in obstructive jaundice: similarities with pregnancy-induced immunosuppression

Rheumatoid arthritis (RA) is ameliorated during both obstructive jaundice a nd pregnancy. Previous studies of polymorphonuclear leukocyte (PMN) functio n during pregnancy have shown reductions in the stimulated release of arach idonic acid (AA) and leukotriene B-4 (LTB4), and lower NADPH oxidase activi ty. These changes may account for the amelioration of RA. The cause of this reduction in PMN function appears to be a progressive change in circulatin g fatty acids (FA), with a reduction in polyunsaturated FA, predominantly A A. The NADPH oxidase responsible for the respiratory burst has a direct req uirement for polyunsaturated FA, particularly AA. We investigated whether t he same changes in PMN function and FA, occur during obstructive jaundice. Patients with biliary obstructions were investigated before and after surgi cal correction (n=14). Obstructive jaundice caused significant changes in t he proportions of serum and cellular FA. There was a striking reduction in polyunsaturated FA, particularly AA (48% in serum, p<0.001; 42% in PMNs, p< 0.001) and an increase in mono-unsaturated oleic acid (24% in serum, p<0.00 1; 15% in PMNs, p<0.005). Similar changes occurred in mononuclear cell FA. jaundice also caused a significant reduction in PMN function. Respiratory b urst activity was reduced by between 32% and 38% in response to physiologic al and nonphysiological stimuli, and there were similar significant reducti ons in the release of AA and LTB4. These changes in stimulated PMN function were evident whether or not the cells were first primed with tumour necros is factor alpha (TNF alpha). Incubation of PMNs from healthy donors in pool ed serum from patients with obstructive jaundice caused a reduction of 32% in cellular AA and 38% in NADPH oxidase activity. These findings support th e idea that circulating FA can regulate PMN inflammatory responsiveness. Th e FA-induced attenuation in PMN activity in both jaundice and pregnancy may explain their ameliorating effects upon RA.