Effects of Different Blood Purification Methods on Serum Cytokine Levels and Prognosis in Patients With Acute Severe Organophosphorus Pesticide Poisoning

The aim of the present study was to investigate the impact of three different blood purification methods, hemoperfusion (HP), continuous blood purification (CBP), and on‐line high‐volume hemodiafiltration (OL‐HDF), on the survival rate of patients with acute severe organophosphorus pesticide poisoning (ASOPP), as well as on major pro‐inflammatory (interleukin [IL]‐1, IL‐6, tumor necrosis factor‐α [TNF‐α]) and anti‐inflammatory (IL‐10) cytokines in the serum. Eighty‐one ASOPP patients were randomly divided into three groups: HP (N = 23), HP + CBP (N = 26), HP + OL‐HD (N = 32). Serum IL‐1, IL‐6, TNF‐α, and IL‐10 levels were assessed by ELISA before treatment and at 24 and 48 h post‐treatment and survival rates were determined. Patient survival rate was significantly higher in OL‐HDF and CBP treated patients compared with HP group (P < 0.05). A significantly greater clearance effect in serum IL‐1, IL‐6, and TNF‐α levels at 24 and 48 h post‐treatment was observed in CBP and OL‐HDF groups compared with the HP group (P < 0.05). The levels of serum anti‐inflammatory cytokine IL‐10 increased significantly in CBP and OL‐HDF groups compared with the HP group (P < 0.05 at 48 h post‐treatment). In addition, OL‐HDF treatment achieved similar changes in serum TNF‐α, IL‐1, IL‐6 and IL‐10 levels as CBP (P > 0.05). Compared with the HP method, CBP or OL‐HDF combined with HP can rapidly clear inflammatory cytokines, reduce systemic inflammatory response syndrome, and improve the survival of ASOPP patients. Compared with CBP, OL‐HDF is an economical and effective method to treat ASOPP with less technical difficulty and more suitability for rural areas and primary hospitals.     

Clinical and psychosocial factors associated with depression and anxiety in Singaporean patients with rheumatoid arthritis

Aim: To assess the frequency of, and factors associated with, depression and anxiety in Singaporean patients with rheumatoid arthritis (RA). Method: One hundred RA patients were recruited in a cross‐sectional study. Socio‐demographics, severity of anxiety and depression, disease activity, levels of serological markers and health‐related quality of life were analyzed. Results: Twenty‐six percent presented with anxiety, 15% with depression and 11% with both. Univariate regression showed that age (P = 0.039), Disease Activity Scale (DAS‐28) (P < 0.001), number of medications (P < 0.001) and rheumatoid factor (RF) (P < 0.001) were positively associated with severity of depression, while income (P = 0.001), education (P = 0.029), self‐perceived social support (P = 0.007), Short form 12 (SF‐12) physical health (P < 0.001) and SF‐12 mental health (P < 0.001) were negatively associated with severity of depression. After adjustment for confounding factors in multivariate regression, income (β = ?0.347, P = 0.018), RF (β = 0.304, P = 0.043) and SF‐12 mental health (β = ?0.501 P = 0.001) remained significantly associated with depression. Univariate regression showed that DAS‐28 (P = 0.009), number of medications (P = 0.004) and RF (P = 0.043) were positively associated with anxiety, while income (P = 0.022), self‐perceived social support (P = 0.04), SF‐12 physical health (P < 0.001) and SF‐12 mental health (P < 0.001) were negatively associated with anxiety. After adjustment for confounding factors, no factors remained significantly associated with anxiety. Conclusion: Low income, high levels of RF and poor mental health were associated with depression in RA. Our findings may help to formulate depression screening strategies. Further research is required to identify the role of RF in depression.     

Brief Report: Inhibition of interleukin‐6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis

Objective

From an immunologic standpoint, the mechanisms by which treatment with tocilizumab (TCZ), a humanized anti–interleukin‐6 (anti–IL‐6) receptor antibody, results in improvement in rheumatoid arthritis (RA) patients are still not fully understood. In vitro studies and studies in mouse models have demonstrated the critical role of IL‐6 in Th17 cell differentiation. Th17 lymphocytes have been shown to be strongly involved in RA pathogenesis, and the purpose of this study was to investigate the effect of IL‐6 blockade on the balance between Th17 cells and Treg cells in patients with active RA.

Methods

Patients with active RA for whom TCZ had been prescribed by a rheumatologist were enrolled in this study. Phenotypic analyses of T cell populations were performed, and the Disease Activity Score in 28 joints (DAS28) was assessed. Serum cytokine levels and other parameters of inflammation were measured before the first infusion and after the third infusion of TCZ (8 mg/kg).

Results

Compared to controls, levels of Th17 cells (CD4+IL‐17+) were increased and Treg cells (CD4+CD25^highFoxP3+) were decreased in the peripheral blood of patients with active RA. The suppressive function of circulating Treg cells was not impaired in patients with active RA. TCZ treatment induced a significant decrease in the DAS28 associated with a significant decrease in the percentage of Th17 cells (from a median of 0.9% to 0.45%; P = 0.009) and an increase in the percentage of Treg cells (from a median of 3.05% to 3.94%; P = 0.0039) in all patients.

Conclusion

This study demonstrates for the first time that inhibition of IL‐6 function by TCZ corrects the imbalance between Th17 cells and Treg cells in patients with RA.

     

Inadequately low serum levels of steroid hormones in relation to interleukin‐6 and tumor necrosis factor in untreated patients with early rheumatoid arthritis and reactive arthritis

Objective

To compare levels of steroid hormones in relation to cytokines and to study levels of cortisol or dehydroepiandrosterone (DHEA) in relation to other adrenal hormones in untreated patients with early rheumatoid arthritis (RA) and reactive arthritis (ReA) compared with healthy controls.

Methods

In a retrospective study with 34 RA patients, 46 ReA patients, and 112 healthy subjects, we measured serum levels of interleukin‐6 (IL‐6), tumor necrosis factor (TNF), adrenocorticotropic hormone (ACTH), cortisol, 17‐hydroxyprogesterone (17‐OH‐progesterone), androstenedione (ASD), DHEA, and DHEA sulfate (DHEAS).

Results

RA patients had higher serum levels of IL‐6, TNF, cortisol, and DHEA compared with ReA patients and healthy subjects, but no difference was noticed with respect to ACTH and DHEAS. However, in RA and ReA patients compared with healthy subjects, levels of ACTH, cortisol, ASD, DHEAS, and 17‐OH‐progesterone were markedly lower in relation to levels of IL‐6 and TNF. Furthermore, the number of swollen joints correlated inversely with the ratio of serum cortisol to serum IL‐6 in RA (R_Rank = −0.582, P = 0.001) and, to a lesser extent, in ReA (R_Rank = −0.417, P = 0.011). In RA patients, the mean grip strength of both hands was positively correlated with the ratio of serum cortisol to serum IL‐6 (R_Rank = 0.472, P = 0.010). Furthermore, in these untreated patients with RA and ReA, there was a relative decrease in the secretion of 17‐OH‐progesterone, ASD, and DHEAS in relation to DHEA and cortisol. This indicates a relative predominance of the nonsulfated DHEA and cortisol in relation to all other measured adrenal steroid hormones in the early stages of these inflammatory diseases.

Conclusion

This study indicates that levels of ACTH and cortisol are relatively low in relation to levels of IL‐6 and TNF in untreated patients with early RA and ReA compared with healthy subjects. The study further demonstrates that there is a relative increase of DHEA and cortisol in relation to other adrenal hormones, such as DHEAS. This study emphasizes that adrenal steroid secretion is inadequately low in relation to inflammation. Although changes in hormone levels are similar in RA and ReA, alteration of steroidogenesis is more pronounced in RA patients than in ReA patients.

     

Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis

Objective

To analyze the frequency, surface phenotype, and cytokine secretion of CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) compared with both healthy control subjects and patients with rheumatoid arthritis (RA).

Methods

Eight‐color flow cytometry was used to analyze the surface phenotype and cytokine production of PBMCs from 20 patients with AS, 12 patients with RA, and 16 healthy control subjects, following stimulation ex vivo with phorbol myristate acetate and ionomycin for 5 hours. Secretion of interleukin‐17 (IL‐17) by PBMCs was measured by enzyme‐linked immunosorbent assay, following stimulation with anti‐CD3/CD28 for 4 days.

Results

The percentages of IL‐17–positive CD4+ T cells and IL‐22–positive CD4+ T cells were increased in the PBMCs of both patients with AS and patients with RA compared with healthy control subjects, whereas there were no differences in the percentages of interferon‐γ (IFNγ)–positive or IL‐10–positive CD4+ T cells. Likewise, concentrations of IL‐17 in supernatants from patients with AS were significantly higher compared with those from healthy control subjects. In patients with RA, the concentrations of IL‐17 were increased but not significantly. There was a correlation between the percentages of IL‐17–positive CD4+ T cells detected in PBMCs and the amounts of IL‐17 in culture supernatants (r = 0.414, P = 0.0034). All IL‐17–producing cells were CD4+CD45RO+; most expressed both CCR6 and CCR4, but only 50% expressed the IL‐23 receptor (IL‐23R). Nevertheless, there was a positive relationship between the percentage of IL‐23R–positive CD4+ T cells and the frequency of IL‐17–positive CD4+ T cells or IL‐22–positive CD4+ T cells (r = 0.57, P < 0.0001 and r = 0.46, P = 0.001, respectively). A significant proportion of cells that produced IL‐17 also produced IL‐22 and IFNγ, but none produced IL‐10.

Conclusion

The frequencies of IL‐17–positive and IL‐22–positive CD4+ T cells were increased in PBMCs from patients with AS and patients with RA, resulting in secretion of higher quantities of IL‐17 by PBMCs following stimulation. These data support the hypothesis that Th17 cells, particularly when present in excess of IL‐10–producing cells, are involved in the pathogenesis of inflammatory arthritis.

     

Serum and synovial fluid leptin levels and markers of inflammation in rheumatoid arthritis

This study was designed to investigate the serum and synovial fluid leptin levels, and inflammatory markers in rheumatoid arthritis (RA) patients. Serum and synovial fluid leptin levels were significantly higher (P > 0.05) in RA patients than control group; RA patients with moderate disease activity (DAS < 2.7) having significantly higher leptin levels (P > 0.05) than those with low disease activity (DAS < 2.7). Leukocytes and erythrocyte sedimentation rate (ESR) were found to be significantly higher in moderate disease activity RA group compared to low activity group (P > 0.05, P < 0.001, respectively). Serum leptin level is found to be independent of age and inflammatory markers. ESR is positively correlated with DAS activity and CRP values. Our finding of no correlation between leptin and BMI shows that regulation of leptinemia is complex, and leptin levels cannot be used to assess RA activity.     

American cutaneous leishmaniasis: In situ immune response of patients with recent and late lesions

TNF‐α, IFN‐γ, IL‐10, IL‐17, CD68 and CD57 were evaluated in biopsies of patients with American cutaneous leishmaniasis living in Sorocaba, Brazil. The analyses were performed considering the time of lesions from 23 patients with recent lesions (Group I) and 19 patients with late lesions (Group II). All patients were infected with Leishmania (Viannia) braziliensis. Immunostaining cells for CD68, CD57, TNF‐ α, IFN‐γ, IL‐10 and IL‐17 were performed by immunohistochemistry. Except for CD68 and IL‐17, the distribution of in situ for CD57, IL‐10, TNF‐α and IFN‐γ showed that patients with recent lesions expressed higher levels than those with late lesions. The comparison of cytokine expression/group showed that IL‐10 was significantly higher than IL‐17 and IFN‐γ (similar data were shown in IL‐17 compared with TNF‐α), suggesting an immunological balance between inflammatory‐anti‐inflammatory agents. This balance was similar for two groups of patients. In conclusion, these data suggested that (i) patients from Group I had recent lesions (in the beginning of chronic phase) compared to those from Group II and (ii) the modulation of inflammatory response in patients with recent American cutaneous leishmaniasis was correlated with IL‐10 expression in skin lesions preventing the development of mucosal forms. The parasite treatment also prevented the evolution of severe forms.     

Identification of patients with chronic obstructive pulmonary disease (COPD) by measurement of plasma biomarkers

Introduction: Inflammation is an important constituent of the pathology of chronic obstructive pulmonary disease (COPD), leading to alveolar destruction and airway remodelling. Objective: The aim of this study was to assess the difference in plasma biomarkers of inflammation between asymptomatic smokers and patients with COPD. Methods: We used commercially available enzyme‐linked immunosorbent assay kits to measure the plasma levels of tumour necrosis factor‐α (TNF‐α), interleukin‐8 (IL‐8), matrix metalloproteinase‐9 (MMP‐9), monocyte chemotactic protein‐1 (MCP‐1), tissue inhibitor of metalloproteinase‐1 (TIMP‐1) and tissue inhibitor of metalloproteinase‐2 (TIMP‐2) on two occasions with a 2‐week interval in patients with COPD (n = 20), asymptomatic smokers (n = 10) and healthy lifelong non‐smokers (n = 10). The participants were characterised clinically, physiologically and by quantitative computed tomography by measuring the relative area of emphysema below ?910 Hounsfield units (RA‐910). Results: The results of the biomarker measurements on the two occasions were highly reproducible. Patients with COPD had significantly higher plasma levels of IL‐8 (P = 0.004) and significantly lower levels of TIMP‐1 (P = 0.02) than smokers and non‐smokers. There was no statistically significant difference between the three groups in the level of TNF‐α, MMP‐9, MCP‐1 and TIMP‐2. The IL‐8/TIMP‐1 ratio correlated significantly with the degree of airway obstruction measured as forced expiratory volume in 1 second (FEV₁) % predicted (r = ?0.47, P < 0.01); with the diffusion capacity (r = ?0.41, P < 0.01); and with the grade of emphysema measured as RA‐910 (r = 0.39, P = 0.01). Conclusion: These findings suggest that the measurement of plasma biomarkers, such as IL‐8/TIMP‐1, may aid to discriminate patients with COPD from smokers at lower risk of developing COPD. Please cite this paper as: Shaker SB, von Wachenfeldt KA, Larsson S, Mile I, Persdotter S, Dahlbäck M, Broberg P, Stoel B, Bach KS, Hestad M, Fehniger TE and Dirksen A. Identification of patients with chronic obstructive pulmonary disease (COPD) by measurement of plasma biomarkers. The Clinical Respiratory Journal 2008; 2: 17–25.     

Anti–interleukin‐6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis: A randomized,double‐blind,placebo‐controlled study

Objective

Proinflammatory cytokines such as tumor necrosis factor (TNF) were demonstrated to inhibit adrenal steroidogenesis in patients with rheumatoid arthritis (RA), and this was particularly evident in the increase in adrenal androgen levels during anti‐TNF therapy. This study investigated the influence on steroidogenesis of an interleukin‐6 (IL‐6)–neutralizing strategy using IL‐6 receptor monoclonal antibodies (referred to as MRA).

Methods

In a placebo‐controlled, double‐blind, randomized study over 12 weeks in 29 patients with RA being treated with prednisolone, 13 of whom received placebo and 16 of whom received 8 mg MRA/kg body weight, the effects of MRA on serum levels of adrenocorticotropic hormone (ACTH), cortisol, 17‐hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione (ASD), estrone, and 17β‐estradiol, as well as their respective molar ratios, were determined.

Results

MRA therapy markedly improved clinical signs of inflammation (the erythrocyte sedimentation rate, swollen joint score, and Disease Activity Score in 28 joints). Serum levels of ACTH and cortisol and the molar ratio of cortisol to ACTH did not change. Although serum levels of DHEA and DHEAS remained stable during therapy, the DHEAS:DHEA molar ratio significantly decreased in treated patients (P = 0.048). Serum levels of ASD as well as the ASD:cortisol and ASD:17OHP molar ratios increased in MRA‐treated patients (minimum P < 0.004). Serum levels of estrone and 17β‐estradiol did not change. but the estrone:ASD molar ratio (an indicator of aromatization) decreased during 12 weeks of MRA treatment (P = 0.001).

Conclusion

Neutralization of IL‐6 increases secretion of biologically active adrenal androgens in relation to that of precursor hormones and estrogens. This is another important indication that proinflammatory cytokines interfere with adrenal androgen steroidogenesis in patients with RA.

     

The role of sleep problems in central pain processing in rheumatoid arthritis

Objective

Among rheumatoid arthritis (RA) patients, the intensity of pain may be out of proportion to the severity of peripheral inflammation. This observation suggests that mechanisms of central nervous system pain amplification, such as diminished conditioned pain modulation (CPM), may play a role in enhancing pain perception among some RA patients. This study was undertaken to examine the level of CPM, pressure–pain threshold, and pressure–pain tolerance among RA patients compared to healthy controls.

Methods

Fifty‐eight female RA patients and 54 age‐matched female control subjects without chronic pain underwent quantitative sensory testing (QST) to assess CPM levels, pressure–pain thresholds, and pressure–pain tolerance levels. CPM was induced using a cold water bath, and the pain threshold (when patients first felt pain) and pain tolerance (when pain was too much to bear) were assessed with an algometer. Associations between RA and each QST outcome were analyzed using linear regression. Sleep problems, mental health, and inflammation were assessed as mediators of the relationship between RA and QST outcomes.

Results

The median CPM level was 0.5 kg/cm² (interquartile range [IQR] −0.1, 1.6) among RA patients, compared to a median of 1.5 kg/cm² (IQR −0.1, 2.5) among controls (P = 0.04). RA patients, compared to controls, had a lower pain threshold and lower pain tolerance at the wrists (each P ≤ 0.05). In addition, RA patients had greater problems with sleep, pain catastrophizing, depression, and anxiety (P < 0.0001 versus controls). Results of mediation analyses suggested that low CPM levels might be attributed, in part, to sleep disturbance (P = 0.04).

Conclusion

RA patients have impaired CPM when compared to pain‐free control subjects. Sleep problems may mediate the association between RA and attenuated CPM.

     

Correlation between serum biomarkers and BODE index in patients with stable COPD

Background and objective: The BODE index, based on BMI, obstructive ventilatory impairment, dyspnoea scale and exercise capacity, has been used to evaluate the severity of patients with COPD. However, the correlations between serum biomarkers and the BODE index in patients with stable COPD are not widely studied. This study evaluated potential serum biomarkers for their ability to identify smokers with COPD and reflect disease severity. Methods: A comparative study was conducted of 100 clinically stable COPD patients and 50 matched healthy smokers and the difference in levels of biomarkers between the COPD patients and healthy smokers was measured. Serum inflammatory mediators measured were growth‐related oncogene‐α (GRO‐α), IL‐8, tumour necrosis factor‐α (TNF‐α), matrix metalloproteinase‐9 (MMP‐9) and monocyte chemoattractant protein‐1 (MCP‐1). Variables included age, pack‐years, current or ex‐smoker status, inhaler or oral steroid use and BODE index components, including airflow obstruction, the distance walked in 6MWD, modified Medical Research Council (MMRC) dyspnoea scale and BMI. The association between serum biomarkers and the components of the BODE index was assessed in the COPD patients. Results: The level of serum MCP‐1 was significantly different between the COPD group and the healthy smoker group (P = 0.003). Significant results in univariate and multivariate analysis of the association between biomarkers and BODE components were: serum MCP‐1 correlated with FEV₁% and 6MWD; serum IL‐8 and GRO‐α correlated with steroid use; serum TNF‐α correlated with steroid use and FEV₁%; and serum MMP‐9 correlated with MMRC dyspnoea scale. Conclusions: No single specific serum inflammatory mediator was completely correlated with BODE variable parameters in patients with stable COPD. Serum MCP‐1 may be an important biomarker for identifying COPD subjects from healthy smokers and classifying COPD severity.     

Functional and work outcomes improve in patients with rheumatoid arthritis who receive targeted,comprehensive occupational therapy

Objective

Work disability is a serious consequence of rheumatoid arthritis (RA). We conducted a 6‐month, prospective randomized controlled trial comparing assessments of function, work, coping, and disease activity in employed patients with RA receiving occupational therapy intervention versus usual care.

Methods

Employed patients with RA with increased perceived work disability risk were identified by the RA Work Instability Scale (WIS; score ≥10). Patients were stratified into medium‐ (score ≥10 and <17) and high‐risk (≥17) groups, then randomized into occupational therapy or usual care groups. Assessments were conducted at baseline and 6 months. The primary outcome was the Canadian Occupational Performance Measure (COPM), a standardized patient self‐report of function. Other outcomes included the disability index (DI) of the Health Assessment Questionnaire (HAQ); Disease Activity Score in 28 joints (DAS28); RA WIS; EuroQol Index; visual analog scales (VAS) for pain, work satisfaction, and work performance; and days missed/month. Independent sample t‐tests and Mann‐Whitney U tests were used.

Results

We recruited 32 employed patients with RA. At baseline the groups were well matched. At 6 months the improvement in the occupational therapy group was significantly greater than that in the usual care group for all functional outcomes (COPM performance P < 0.001, COPM satisfaction P < 0.001, HAQ DI P = 0.02) and most work outcomes (RA WIS [P = 0.04], VAS work satisfaction [P < 0.001], VAS work performance [P = 0.01]). Additionally, Arthritis Helplessness Index (P = 0.02), Arthritis Impact Measurement Scales II pain subscale (P = 0.03), VAS pain (P = 0.007), EuroQol Index (P = 0.02), EuroQol global (P = 0.02), and DAS28 (P = 0.03) scores significantly improved.

Conclusion

Targeted, comprehensive occupational therapy intervention improves functional and work‐related outcomes in employed RA patients at risk of work disability.     

Anti–interleukin‐6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis

Objective

To investigate whether interleukin‐6 (IL‐6) is a regulator of vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA).

Methods

Serum VEGF levels in RA patients were assayed before and after 8 weeks or 24 weeks of maintenance therapy with humanized anti–IL‐6 receptor monoclonal antibody (anti–IL‐6R mAb). VEGF secreted by RA synovial fibroblasts cultured in the presence of IL‐6, IL‐1β, and/or tumor necrosis factor α (TNFα) was measured. The inhibitory effect of anti–IL‐6R mAb, recombinant IL‐1 receptor antagonist (IL‐1Ra), and anti‐TNFα mAb on VEGF production was also examined.

Results

Serum VEGF levels in RA patients before anti–IL‐6R mAb therapy were significantly higher than those in healthy controls (P < 0.0005). Treatment of RA patients with anti–IL‐6R mAb normalized serum VEGF levels. In the in vitro study, IL‐6 and IL‐1β each induced a slight amount of VEGF production in synovial cells, but TNFα did not. Although VEGF‐inducing activity of these cytokines was not remarkable when they were added alone, IL‐6 acted synergistically with IL‐1β or TNFα to induce VEGF production. There was no synergistic effect between IL‐1β and TNFα. In the presence of all of these cytokines, anti–IL‐6R mAb eliminated the synergistic effect of IL‐6, IL‐1β, and TNFα, while IL‐1Ra or anti‐TNFα mAb did not.

Conclusion

Anti–IL‐6R mAb therapy reduced VEGF production in RA. IL‐6 is the pivotal cytokine that induces VEGF production in synergy with IL‐1β or TNFα, and this may be the mechanism by which IL‐6 blockade effectively suppresses VEGF production in synovial fibroblasts.

     

Association of the CagA status of Helicobacter pylori and serum levels of interleukin (IL)‐17 and IL‐23 in duodenal ulcer patients

OBJECTIVE: It has been reported that the cytotoxin‐associated gene A (cagA+) H. pylori strains induce severe gastric mucosal inflammation. The aim of this study was to investigate the association of the virulence factor CagA with IL‐17 and IL‐23 serum levels in duodenal ulcer (DU) patients and H. pylori‐infected asymptomatic (AS) carriers. METHODS: In total, 45 H. pylori‐infected DU patients were enrolled to study: 23 tested positive for the anti‐CagA antibody (anti‐CagA+) and 22 tested negative for the anti‐CagA antibody (anti‐CagA‐), 30 were AS carriers (15 were anti‐CagA+ and 15 were anti‐CagA‐) and 15 were healthy uninfected participants (as a control group). The IL‐17 and IL‐23 serum levels of participants were measured by enzyme‐linked immunosorbent assay method. RESULTS: The mean IL‐17 levels in DU patients were significantly higher than those in AS and control groups (P < 0.001 and P < 0.0001 respectively). In the DU group, the mean IL‐17 levels in participants testing positive for anti‐CagA (10.84 ± 5.79 pg/mL) were significantly higher than those observed in participants testing negative for anti‐CagA (7.65 ± 4.74 pg/mL; P < 0.05). The mean IL‐23 levels in the DU and AS groups were significantly higher than in the control group (P < 0.02 and P < 0.03 respectively) but were not significantly different in participants testing positive and negative for anti‐CagA. CONCLUSION: These results showed higher IL‐17 and IL‐23 serum levels in H. pylori‐infected participants than in the control group. In the DU group the expression of IL‐17 was influenced by the CagA factor.     

Clinical significance of IL-18, IL-15, IL-12 and TNF-α measurement in rheumatoid arthritis

The aim of the study was to evaluate the clinical significance of serum (S) and synovial fluid (SF) interleukin (IL)-18, IL-15, IL-12 and the tumor necrosis factor alpha (TNF-α) measurements in relation to laboratory and clinical measures of disease activity of patients with active rheumatoid arthritis (RA). Sixty-four patients with RA and 25 patients with osteoarthritis (OA) were included in this study. RA activity was determined using the Disease Activity Score (DAS) 28 index. Concentrations of IL-18, IL-15, IL-12 and TNF-α were measured by ELISA. Serum C-reactive protein (CRP) levels were also determined. Cross-sectional correlations between S and SF levels of cytokines and values of DAS 28 index were calculated. The results have shown that IL-18, IL-15, IL-12 and TNF-α levels in S and SF of patients with RA were significantly higher than the levels obtain from patients with OA (p<0.01). Significantly higher levels of IL-18, IL-15 and TNF-α were found in the SF compared to the S of patients with RA (p<0.01). Significantly higher S and SF levels of all four cytokines and serum CRP values were found in RA patients with high disease activity (DAS 28>5.1) compared to those with mild (DAS 28>3.2) and low disease activity (DAS 28>2.6) (p<0.01). Serum and SF concentrations of all four cytokines positively correlated with DAS 28 index values, i.e., disease activity. A poor correlation was found for S and SF IL-12 whereas the highest coefficient of correlation was found for SF IL-18 (r=0.879, p<0.01), and SF TNF-α (r=0.827, p<0.01) and disease activity in this study. Strong correlation was found between SF TNF-α and SF IL-18 levels (r=0.732, p<0.01). In conclusion, SF IL-18 and TNF-α levels in RA patients are good indicators of disease activity. The results obtained support the use of the DAS in clinical practice as a reliable method in assessing disease activity in RA patients.     

Pain sensitivity and pain reactivity in osteoarthritis

Objective

To assess experimental pain sensitivity and compare the inflammatory response to pain in 26 osteoarthritis (OA) patients and 33 age‐ and sex‐matched controls from the general population in order to examine the nature of the association between pain and inflammation in OA.

Methods

The participants underwent psychophysical pain testing to assess pain sensitivity in response to heat, cold, and mechanical stimuli. Blood samples were taken at baseline and at 4 time points after testing to determine the effect of acute pain on C‐reactive protein (CRP), interleukin‐6 (IL‐6), IL‐1β, and tumor necrosis factor α levels.

Results

OA patients had lower pressure pain thresholds (P ≤ 0.003) and higher heat pain ratings (P ≤ 0.04) than controls across multiple body sites. OA patients had higher CRP levels than controls (P = 0.007). CRP levels did not change in response to pain testing. Although not statistically significant, OA patients tended to have higher IL‐6 levels than controls (P = 0.12). IL‐6 levels increased after pain testing in OA patients and controls (P < 0.0001), but the amount of increase was not different between the 2 groups. Among OA patients, heightened pain sensitivity was associated with elevated CRP and IL‐6 levels (P ≤ 0.05).

Conclusion

Compared with controls, OA patients are more sensitive to experimental pain at multiple body sites. IL‐6 levels in OA patients and controls exhibited reactivity to acute painful stimuli, increasing at similar rates after psychophysical pain testing.     

Efficacy of High‐Throughput Leukocytapheresis for Rheumatoid Arthritis With a Reduced Response to Infliximab

Infliximab (INF), a tumor necrosis factor‐alpha (TNF‐α) inhibitor, is an effective drug for patients with rheumatoid arthritis (RA). However, some patients receive no clinical benefit, or the agents gradually lose their effect. Five sessions of high‐throughput leukocytapheresis (LCAP) were given at a frequency of once a week using a Cellsorba CS‐180S to four patients with a reduced response to INF. The clinical response to LCAP was evaluated using the 28‐joint disease activity score with C‐reactive protein (DAS28‐CRP) and with the erythrocyte sedimentation rate (DAS28‐ESR). DAS28‐CRP decreased significantly from 5.8 ± 0.6 before LCAP to 3.9 ± 0.7 (P = 0.0182) at 1–2 weeks after completion of five sessions of LCAP, and DAS28‐ESR decreased significantly from 6.4 ± 0.6 to 4.6 ± 0.5 (P = 0.0267). Moreover, all patients had a moderate response according to the European League Against Rheumatism (EULAR) response criteria. The effect of LCAP continued for at least 6 months after its completion in all patients, with no changes in any of their concomitant drugs, and the effect was maintained for at least 1 year in three of the four patients. These results indicate that LCAP is a useful treatment for RA patients with a reduced response to INF.     

Serum oxidized low-density lipoproteins in rheumatoid arthritis

Objective The aim of this study was to measure serum oxidized low-density lipoprotein (Ox-LDL) levels in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and to identify any association with clinical variables.Methods We studied 126 female patients (27 with active RA, 27 with inactive RA, 72 with SLE). One hundred fifteen age-matched healthy women (76 for RA, 39 for SLE) with no clinical or laboratory evidence of disease served as normal controls. Serum Ox-LDL levels were measured with a commercial enzyme-linked immunosorbent assay kit (Mercodia, Sweden).Results The serum Ox-LDL levels were significantly higher in patients with active RA (P<0.05) or SLE (P<0.01) than age-matched controls and significantly higher in patients with active RA than with inactive RA (P<0.01). The levels of serum total cholesterol and LDL were significantly lower in patients with RA than in age-matched controls (P<0.01). There was no correlation among serum Ox-LDL levels and inflammatory markers (erythrocyte sedimentation rate, C-reactive protein) or rheumatoid factors in patients with RA.Conclusions Compared with healthy women, those with SLE or active RA had increased serum Ox-LDL levels, which may contribute to the increased risk of cardiovascular disease in this patient group.