No abstract

Two-dimensional (2-D) gel analysis was used to examine differences in the levels of 19 plasma proteins: before and after an acute inflammatory reaction (parenteral typhoid vaccination) in normal subjects, between rheumatoid arthritis (RA) patients and normals and in RA patients treated with tenidap (120 mg) and piroxicam (20 mg). Typhoid vaccination increased levels of SAA, haptoglobin alpha1, haptoglobin alpha2, haptoglobin beta and alpha1-anti-chymotrypsin but decreased transthyretin and apolipoprotein E. In RA patients, serum amyloid A (SAA), haptoglobin alpha2, haptoglobin beta, alpha1-antichymotrypsin and C3 proactivator levels were elevated while apolipoprotein A-I, apolipoprotein A-IV, transthyretin, Gc-globulin, alpha2-HS glycoprotein, alpha2-macroglobulin and alpha1-B glycoprotein levels were decreased, compared to normals. Compared to piroxicam, tenidap lowered levels of alpha1-antiprotease and SAA but raised the levels of transthyretin, Gc-globulin, alpha2-HS-glycoprotein and alpha2-macroglobulin in RA patients. C-reactive protein (CRP) could not be quantified on 2-D gels but, when measured by rate nephelometry, levels were reduced after treatment with tenidap compared to piroxicam. The general pattern of the acute phase protein response to an acute inflammatory response to typhoid vaccination is similar to that in the chronic inflammatory condition, RA. The impact of tenidap on both positive and negative acute-phase proteins in RA patients could clearly be distinguished from that of piroxicam.

No abstract

Intraperitoneal injection of inflammatory agents in the mouse and rat causes plasma protein and leukocyte extravasation into the peritoneal cavity. Following an intraperitoneal injection of zymosan A, the milky spots of the omentum were the only abdominal sites detected where intravenously administered Monastral Blue labeled interendothelial cell gaps responsible for plasma extravasation. In addition, when colored microspheres were intraventricularly administered to quantify blood flow, the omentum was the only abdominal organ which showed an increase in blood flow during zymosan A peritonitis. A combination of light and electron microscopy, plus measurement of myeloperoxidase activity (a marker of neutrophil accumulation) demonstrated that the omental milky spots are the major route through which leukocytes migrate into the peritoneal cavity. Identical structures in the pleura likewise are the sites of protein leakage into the pleural cavity. In contrast, selective sites of protein and cellular extravasation could not be detected in the synovial lining of the inflamed knee joint.

Intraperitoneal injection of zymosan (1 mg in 0.5 ml saline) in mice induces a transient writhing response accompanied by the synthesis of small amounts of prostaglandin E2 (PGE2, < 2 ng) and larger amounts of PGI2 (200 ng per mouse), measured as its non‐enzymatic breakdown product, 6‐keto‐PGF1α. Although both centrally‐acting analgesics (morphine, clonidine) and prostaglandin biosynthesis inhibitors (aspirin, indomethacin, ibuprofen) blocked the writhing response to intraperitoneal injection of zymosan, only the latter reduced prostaglandin levels in the peritoneal cavity. The writhing response correlated equally well with PGE2 levels and 6‐keto‐PGF1α levels when data from mice treated with centrally‐acting analgesics were excluded. However, intraperitoneal injection of PGI2, but not PGE2, reversed the analgesia induced by indomethacin in zymosan‐injected mice. Centrally‐acting agents, but not ibuprofen, blocked the ability of PGI2 to reverse the analgesic activity of indomethacin. PGI2 (2 μg per mouse), injected intraperitoneally in otherwise untreated mice, induced writhing. These data indicate that PGI2 is the prostaglandin involved in mediation of the writhing response to zymosan and that prostaglandin biosynthesis inhibitors, but not centrally‐acting analgesics, exert their analgesic activity by reducing the peritoneal level of PGI2. It is possible that PGI2 may have the ability to stimulate pain receptors directly in the mouse peritoneal cavity, in addition to its previously recognized ability to sensitize pain receptors to other pain‐producing stimuli.