An Investigation into Possible Anti-inflammatory Plasma Proteins in Arthritis

Abstract

1. It was confirmed that there are considerable overall changes in the levels of serum proteins in rats with adjuvant-induced arthritis. The concentrations of alpha-globulins and beta-globulins were found to increase whilst the concentrations of albumin decreased. These changes paralleled the severity of the inflammation. Cortisol administration reduced both the inflammation and appeared to normalise the levels of serum proteins. 2. Protease levels were elevated in the serum of adjuvant-induced arthritic rats and closely corresponded with increased lysosomal acid phosphatase levels. 3. The levels of the antiproteases, alpha-1-macroglobulin and alpha-2-acute phase globulin were increased during adjuvant-induced arthritis in the rat; but the trypsin inhibitory capacity (TIC) of the sera was decreased. Cortisol elevated the TIC levels of both normal and adjuvant arthritic rats and this may reflect an anti-inflammatory action of this drug. 4. A human fraction enriched with alpha-1-antitrypsin was found not to have anti-inflammatory activity in the model of carrageenan-induced oedema in the rat. 5. The transcortin levels were found to fall in both male and female rats with adjuvant-induced arthritis during the onset of chronic inflammation. The onset and severity of the disease was similar for both male and female rats despite the increased transcortin levels found in female rats. 6. It was confirmed that dimethyl nitrosamine reduces the severity of adjuvant-induced arthritis and carrageenan-induced oedema in the rat. Saline extracts of livers from dimethyl nitrosamine treated rats were found to have anti-inflammatory activity in carrageenan-induced oedema in the rat. TIC levels were found to be increased in both saline liver extracts from dimethyl nitrosamine treated rats and the serum of dimethylnitrosamine treated rats. 7. A number of non-steroidal anti-inflammatory drugs were tested, at therapeutic concentrations, and found not to influence the stability of transcortin-bound 1,2-H-cortisol in human plasma. Therefore it appears that non-steroidal anti-inflammatory drugs do not act by causing the release of cortisol from its binding sites on transcortin.