LIPOPROTEIN-LIPASE IN RELATION TO INFLAMMATORY ACTIVITY IN RHEUMATOID-ARTHRITIS

Objective. To evaluate the impact of chronic inflammation on lipoprote in lipase (LPL) levels and triglyceride metabolism in patients with rh eumatoid arthritis(RA). Design. Plasma levels of LPL activity and mass before and after heparin were determined in post-menopausal women wit h active RA and in controls. The results were related to lipid levels and inflammatory variables. The LPL activity and mass together with tr iglyceride levels were also measured before and 6 h after an oral fat load. Setting. The study was performed on in- and out-patients at a Un iversity Rheumatology clinic. The controls came from the same referenc e area. Subjects. Altogether 17 consecutive postmenopausal female pati ents with RA and 16 age and sex matched controls were enrolled for the initial determination of LPL. Fifteen of the patients and 15 of the c ontrols agreed to take part in the fat load. Of these, one patient and one control were excluded. Main outcome measures. LPL determination: basal levels and post-heparin levels of LPL activity and mass. Correla tions between LPL and blood lipids (cholesterol, triglycerides), lipop rotein levels (high density lipoprotein, HDL: low density lipoprotein, LDL), erythrocyte sedimentation rate (ESR) acute phase proteins (oros omucoid, haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor alpha, TNF-alpha; interleukin 1 beta, IL-1 beta; and interleuki n-6, IL-6). Fat tolerance test: LPL activity, mass and triglyceride le vels before and 6 h after a per oral fat load. Results. Pre-heparin LP L mass (P < 0.01) and activity (P < 0.01) were significantly lower in the rheumatoid patients. Pre-heparin LPL mass showed no correlation to the lipid levels, but an inverse correlation to several inflammatory parameters; it was significant for orosomucoid (r(s) = -0.63, P< 0.05) and C-reactive protein (CRP) (r(s) = -0.54, P < 0.05) and close to si gnificant for haptoglobin (r(s) = -0.48, P = 0.087) and IL-6 (r(s) = - 0.52, P = 0.061). Six hours after a lipid load the LPL activity and ma ss were significantly lower in RA (P < 0.05 and P < 0.01, respectively ) but the triglyceride level was not significantly different compared to controls. Conclusion. An inverse relationship exists between inflam matory status and pre-heparin LPL mass. Pre-heparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This has been shown to hinder the uptake of remnant lipoprotein particles through competition with lipoprotein bound dimeric LPL for the LDL receptor-related prote in (LRP receptor) on hepatocytes and macrophages in culture. A decreas e of the level of monomeric LPL in plasma may thus be beneficial for r emnant catabolism. The same mechanism may on the other hand increase m acrophage uptake of lipids. This may not affect global lipid metabolis m but may be important in driving the atherosclerotic process in the v essel wall.