Phospholipase activity in synovial fluid from patients with rheumatoid arthritis, osteoarthritis and crystal-associated arthritis.

Phospholipase activity was assayed in cell-free synovial fluid (SF) from patients with rheumatoid arthritis (RA, n = 28), osteoarthritis (OA, n = 10), and crystal-associated arthritis (C, n = 7) by measuring the release of either [14C]oleic acid or [3H]arachidonic acid from radiolabeled E. coli phospholipids. Activity measured by oleic acid release was not significantly different between the three groups of patients (RA = 571 +/- 43.3, OA = 460 +/- 54.7 and C = 718 +/- 162.6 pmol/min/mg). Arachidonic acid release was significantly (p less than 0.005) less in OA (31 +/- 7.3) than RA (61 +/- 4.7) which was similar to C (58 +/- 17.6 pmol/min/mg). Arachidonic acid release correlated significantly with the SF white blood cell count (r = 0.483, p less than 0.01). This study shows the importance of the type of substrate used to measure phospholipase activity and indicates that differences in the capacity to release arachidonic acid may exist between RA and OA disease states.

Phospholipid metabolism in polymorphonuclear leukocytes from rheumatoid arthritis patients: effects of non-steroidal anti-inflammatory agents and clotrimazole.

Arachidonic acid (AA) metabolism and phospholipase A2 (PLA2) activity were measured in the peripheral blood polymorphonuclear leukocytes (PMNL) from ten patients with rheumatoid arthritis (RA) on treatment with various non-steroidal anti-inflammatory agents (NSAIA). AA metabolism and PLA2 activity were measured both initially and after treatment with either placebo or Clotrimazole, a broad spectrum anti-mycotic agent, as a possible anti-rheumatic drug. AA metabolism was also measured in PMNL from ten patients with active RA untreated with any NSAIA and ten normal volunteers. Using 3H-AA prelabeled cells, we show that there was a significantly higher (P less than 0.025) production of 3H-LTB4 in response to stimulation with the calcium ionophore A23187 in untreated RA patients than in normal volunteers (mean +/- S.D.:4.8 +/- 1.6% and 3.1 +/- 1.0%, respectively). The production of 3H-LTB4 by PMNL from patients on NSAIAs was less elevated (mean +/- S.D.:4.1 +/- 1.5%) and was not significantly different from normal controls. Concurrently we examined PLA2 activity in PMNL-sonicates from ten of our study patients using autoclaved [14C]oleate-labeled E. coli biomembranes as an exogenous substrate. Using linear regression analysis, we demonstrate a significant correlation between in vitro PLA2 activity and the release of 3H-AA from the cellular phospholipids (deacylation) in response to A23187 stimulation (r = -0.526, P less than 0.025). We also demonstrate significant correlations between the overall clinical state of the RA patient, as evaluated by a modified rheumatoid activity index (MRAI), and both the release of 3H-AA from the cellular phospholipids and its production of total [3H]eicosanoids (r = -0.557, P less than 0.025 and r = 0.644, P less than 0.005, respectively). This data suggests that: PLA2 activity may, in part, account for the higher generation of LTB4 by RA PMNL; NSAIAs may be capable of modulating this abnormality; and Clotrimazole may affect the clinical or laboratory data of RA patients already on treatment with NSAIA.

Effects of psychological therapy on pain behavior of rheumatoid arthritis patients. Treatment outcome and six-month followup.

A randomized clinical trial was performed to evaluate a psychological treatment intervention and a social support program, compared with a control program in which no adjunct treatment was rendered, and their effects upon pain behavior, affect, and disease activity of 53 patients with rheumatoid arthritis. The psychological intervention produced significant reductions in patients' pain behavior and disease activity at posttreatment. Significant reductions were also observed in trait anxiety at posttreatment and 6-month followup. Relaxation training may have been the most important component of the psychological intervention. The social support program produced a significant reduction in trait anxiety only at posttreatment. This is the first well-controlled study to demonstrate reduced pain behavior, disease activity, and trait anxiety following psychological treatment.

Psychological approaches to the management of arthritis pain.

The present review examines the literature regarding the efficacy of cognitive-behavioral and other self-control interventions in helping arthritis patients reduce their pain and functional disabilities. The evidence indicates that self-control interventions have produced significant and positive changes in the pain and functional disabilities of patients with rheumatoid arthritis and arthritis secondary to hemophilia. However, the literature suffers from deficiencies with regard to the use of small subject samples; inadequate control procedures and follow-up assessments; failure to demonstrate that positive outcomes are related to changes in subjects' covert experiences or control of physiological variables; and reliance upon self-report measures of outcome. The review is followed by a description of a multidisciplinary study of the efficacy of a biofeedback-assisted, cognitive-behavioral group therapy program for rheumatoid arthritis patients that features several methodological improvements relative to previous investigations. The preliminary outcome data show that the cognitive-behavioral intervention is associated with reductions in pain behavior and self-reports of pain and disability. It is concluded that, although the self-control interventions have shown promising results, psychologists must demonstrate positive and reliable outcomes among large numbers of arthritis patients over extended periods of time if the interventions are to be viewed as credible by rheumatologists.

Induction of autoantibody-producing cells after the coculture of haptenated and normal human mononuclear leukocytes.

The coculture of normal human peripheral blood mononuclear leukocytes (PBL) and autologous mononuclear leukocytes coupled to the trinitrophenyl (TNP) hapten (TNP-PBL) was found to induce a polyclonal activation of antibody-producing cells. The polyclonal activation of antibody-producing cells was demonstrated by detecting the induction of cells producing antibody to sheep red blood cells using a complement-dependent, direct, hemolytic plaque-forming cell (PFC) assay. A ratio of four normal to one haptenated mononuclear leukocyte was found to be optimal for inducing the polyclonal activation of antibody-producing cell in these cultures. The plaque-forming cells assay in these experiments utilized monolayers of indicator red cells. Further evidence for the polyclonal induction of antibody-producing cells by TNP-PBL was provided by demonstrating PFC on monolayers of not only sheep red blood cells, but also autologous human red cells, bromelain-treated autologous red cells, TNP-coupled human and sheep red cells, and human autologous red cells coupled to human heat-aggregated IgG with chromic chloride. Thus cells secreting antibody to TNP, human red cells, and human IgG were induced. Anti-IgG and anti-human red cell-producing cells were first detected on Day 2 of culture and were still present on Day 9. Mononuclear leukocytes altered by chemical haptenation polyclonally stimulate normal mononuclear leukocytes to become antibody-producing cells. This polyclonal stimulation of antibody-producing cells includes cells producing antibodies to human IgG and human autologous red blood cells suggesting that autoantibody-producing cells are induced.