Studies on the Modification of the Acute Phase Response in Ma

Methods for several positive and negative acute phase proteins were developed using a Hyland LAS-R nephelometer. The proteins measured were C-reactive protein, alpha1-antichymotrypsin, alpha1-antitrypsin, alpha1-acid glycoprotein, haptoglobin, alpha2 -macroglobulin, albumin, and prealbumin. Using these methods, the effects were studied of an elevated environmental temperature (28°C) on the concentrations of proteins following elective upper gastrointestinal tract surgery. A control group of patients was nursed at a temperature of 20°C. Urine excretion of nitrogen, 3-methylhistidine, cortisol, 17-hydroxycorticosteroids, noradrenaline, and adrenaline was also measured.;All patients demonstrated an acute phase response which corresponded closely to that described in previous studies, but exposure to elevated temperatures did not affect the magnitude of the changes in serum proteins, nitrogen or 3-methylhistidine excretion, or the excretion of catecholamines. There were significant decreases in urine volume and in the excretion of cortisol and 17-hydroxycorticosteroids.;To improve the precision and sensitivity of the C-reactive protein assay, an immunoradiometric assay was developed. An antibody obtained from Seward Laboratories was coupled to microparticulate cellulose with 1,1'carbonyldiimidazole. A second antibody obtained from Atlantic Antibodies was immunopurified using pure C-reactive protein, also coupled to cellulose, and labelled with 125I. Sample was incubated with the labelled antibody for two hours, after which the solid-phase antibody was added and incubation continued with agitation for a further two hours. The cellulose was washed, and bound iodine was counted. The assay correlated well with radial immunodiffusion, EMIT, and nephelometric methods, and the precision was good (between batch precision 11.9% at a level of 35.4 mg/1). The sensitivity of the method was 5 mug/1.;The effect of treating patients suffering from rheumatoid arthritis with either injectable gold (gold sodium thiomalate) or oral gold (auranofin) was compared with treatment with placebo over a period of 48 weeks. Concentrations of acute phase proteins were measured by immunonephelometry and C-reactive protein was measured by the immunoradiometric method. A number of clinical measurements were also carried out for comparison purposes (pain score, duration of morning stiffness, grip strength, and articular index). All of the acute phase proteins were decreased by active treatment, though oral gold was less effective than parenteral gold. C-reactive protein and haptoglobin were decreased to the greatest extent by treatment. The most effective proteins for the detection of active disease before treatment were C-reactive protein and alpha1-antichymotrypsin.;In a preliminary attempt to develop an immunoassay for interleukin 1, peptides chosen from the published amino acid sequence of interleukin 1B, the major form secreted by macrophages, were synthesised chemically. Polyclonal antisera were raised in rabbits against these peptides. It was found that high titre antisera could be produced against peptides corresponding to both the N terminus and the C terminus of interleukin 1. However, recombinant interleukin 1 did not bind avidly to the antisera directed against the N terminus, possibly because of modifications introduced during the synthesis of the recombinant material.;It is hoped that it will be possible to develop an immunoassay for interleukin 1 using these antisera, and that they will be used for its purification and for histochemical studies. These developments should lead to a greater understanding of the role of interleukin 1 in the acute phase reaction. (Abstract shortened by ProQuest.).