On individual reference intervals based on a longitudinal study of plasma proteins and lipids in healthy subjects, and their possible clinical application.

In a longitudinal study, we determined interindividual and intra-individual variation in 20 plasma proteins and lipids and in other blood constituents by analysis of variance. Blood from 20 healthy subjects was sampled monthly for six months, a rigorous blood-sampling technique being applied. The mean proportion of interindividual variation differed for each blood constituent, ranging from 22 to 91% of the total variation. The possible clinical application of individual reference intervals of this homeostatic model was demonstrated by the fact that they were exceeded in individual cases of upper respiratory tract infection. Concordance between individual reference intervals in healthy controls and in patients--as exemplified in two chronic diseases, multiple sclerosis and chronic inactive pyelonephritis--suggests that the use of individual intervals in (chronic) disease is valid, even when derived from healthy persons. Additionally, sex- and age-related differences were significant for some constituents.

Interaction of lipopolysaccharides with plasma high-density lipoprotein in rats.

The method of crossed immunoelectrophoresis was used to investigate early changes in plasma proteins of rats treated with lipopolysaccharide (LPS). Intravenous injection of a smooth (S)- and a rough (R)-form preparation led to alterations in the high-density lipoprotein (HDL) precipitation peak. The changes were dose dependent and characteristic for each LPS. The changes were identified as being due to the formation of a complex of LPS with HDL, the complex of the S-form LPS with HDL migrating slower and that of the R-form LPS with HDL migrating faster than free HDL. The fate of the complex was followed in the plasma of injected rats, and it was shown that the R-form LPS complex disappeared after several hours, whereas the S-form LPS complex was still partly present after 2 days. Plasma clearance studies, carried out with 14C-labeled LPS, revealed similar differences in the rate of elimination of the two LPSs. In both cases the time of clearance resembled that of the disappearance of LPS-HDL complex. These results may indicate that HDL represents a transport protein for LPS in plasma to organs of clearance or to other cellular targets.

Host resistance to lipopolysaccharides in the pathogenesis of multiple sclerosis and membranoproliferative glomerulonephritis.

Host resistance against bacterial lipopolysaccharides (L.P.S.) and especially against its toxic part lipid A has earlier been demonstrated in biological assays. In this paper an aryl-esterase is shown to be associated with alfa-1-lipoprotein (ArE) and is probably responsible for the detoxification of L.P.S. in man. Furthermore C3 is shown to be activitated by L.P.S. From these facts it is suggested that ArE performs the initial degradation of L.P.S. followed by complement activation and trapping of the L.P.S.--complement complex in the reticuloendothelial system. It is postulated that a deficient host response against L.P.S. can be the triggering mechanism in multiple sclerosis due to the lack of ArE in myelin, and that an infectious-agent/L.P.S. syndrome can activate latent infections in connection with a severe hyperreactivity to L.P.S. Preliminary investigations in patients with membranoproliferative glomerulonephritis have shown low levels of ArE in serum. This change, together with the low C3 values in these patients, may result in deficient L.P.S. detoxification and it is suggested that L.P.S. are at least partly responsible for the production of C3 nephritic factor.