Microheterogeneity of acute phase proteins in patients with clinically active and clinically nonactive osteoarthritis

Abstract

Microheterogeneity of two acute phase glycoproteins, alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT), concentrations of AGP, ACT, and C-reactive protein (CRP), and levels of three cytokines: interleukin 1 beta (IL-1-beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were determined in 61 serum samples and 7 synovial fluids (SFs) obtained from patients (n = 61) with osteoarthritis. Using affinity immunoelectrophoresis with concanavalin A (conA), a significant decrease in the reactivity of AGP and ACT with this lectin was found in patients with clinically active osteoarthritis when compared to those with clinically nonactive disease (p < 0.001 and p < 0.05, respectively). There was no increase in the concentration of AGP, ACT, and C-reactive protein (CRP) in the sera examined. In particular, no increase in the serum level of these proteins was found in the patients with clinically active disease. Low concentrations of IL-6 and TNF-alpha were found in most sera and SFs examined. In 6 out of 7 SFs available, IL-6 concentrations were higher than in the respective serum samples but for TNF-alpha the same could be shown in one case only. Low concentrations of IL-1-beta were found in 4 serum samples obtained from patients with clinically active osteoarthritis and in no SF specimen studied. In the entire group, serum level of TNF-alpha correlated weakly with the AGP and ACT reactivity coefficients with conA (r = 0.3634, p < 0.005 and r = 0.3324, p < 0.02, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Autocrine regulation of collagenase 3 (matrix metalloproteinase 13) during osteoarthritis

“…The presence of TNF␣ in synovial fluid and the increase in the densities of TNFRI and TNFRII on OA chondrocytes may imply an important role for this cytokine in the pathogenesis of OA. In support of this hypothesis, increased numbers of chondrocytes that synthesize IL-1␤ and TNF␣ have been found in OA cartilage (15,17). This may reflect the influence of TNF␣ in the synovial fluid, since many cell types in the synovium, such as macrophages, synovial fibroblasts, or chondrocytes themselves, could produce this cytokine.…”

“…In the present experiments, we found that OA chondrocytes constitutively produced mRNA for TNF␣, TNF␤, IL-6, IFN␥, IFN␤, TGF␤1, and TGF␤3. Increased numbers of chondrocytes synthesizing TNF␣, IL-1␤, and IL-6 in OA cartilage also were identified by Hrycaj and coworkers (15) and by Shinmei and coworkers (17). The levels of many of these cytokines are affected by stimulation of the chondrocytes with TNF␣.…”

“…The difference in collagenase expression could be caused by a varying response to cytokine stimulation, due either to an increase in cytokine production locally or to differential sensitivity to cytokine stimulation as a result of an increase in the number of the cytokine receptors per cell (12)(13)(14). Interestingly, although both tumor necrosis factor ␣ (TNF␣) and interleukin-1␤ (IL-1␤) were detected in the serum of patients with clinically active OA, only TNF␣ was found in the synovial fluid (15). The density of the type I receptor for TNF (TNFRI) has been reported to be significantly higher in chondrocytes isolated from OA lesions as compared with chondrocytes from nonaffected areas (16).…”

“…Considering that TNF␣, but not IL-1␤, is known to be present in the synovial fluid of OA patients (15), we chose to investigate the influence of TNF␣ on autocrine cytokine and cytokine in an increase in TNF␣ mRNA itself and in LT␤, but did not affect the level of TGF␤3 mRNA. TGF␤1 and INF␤ mRNA were decreased.…”

Changes of α1-acid glycoprotein microheterogeneity in acute inflammation stages analyzed by isoelectric focusing using serum obtained postoperatively

“…Using CAIE, Con A-reactive dibranched oligosaccharide chains of AGP increase in the sera of early-stage acute inflammation patients [14,16,17] but decrease in the sera of chronic inflammation patients. Examples are severe rheumatoid arthritis [14,15], alcoholic liver cirrhosis [19], pulmonary sarcoidosis [18], and osteoarthritis [20]. This indicates that different inflammatory mediators are involved in the regulation of the degree of branching of AGP in acute and chronic inflammation [21].…”