Effects of nickel sulfate on pulmonary natural immunity in Wistar rats.

This study was designed to investigate the in vivo effect of nickel sulfate on the pulmonary non-specific immune defences. Groups of four male Wistar rats were treated with a single intratracheal instillation of NiSO(4) at different doses: 1, 2, 4 and 8 micromol of NiSO(4) per rat. Control rats received a corresponding instillation of the saline vehicle. The effect of NiSO(4) on the cytotoxic activity of the pulmonary natural killer (NK) cells and alveolar macrophages (AM), as well as the pulmonary production of cytokines such as alpha-tumor necrosis factor (TNF-alpha) and gamma-interferon (IFN-gamma), were examined 1, 2 and 7 days later. Spontaneous NK-cytotoxicity towards mouse-derived tumor cell line, Yac-1 was suppressed 1 day after treatment at doses of 2 micromol/rat and above with only one result significant (P<0.05); 2 days after treatment the suppression was increased with all results significant at the same doses; 1 week after treatment NK activity restoration was observed except for the highest dose, 8 micromol/rat. AM-mediated cytotoxicity towards mouse-derived tumor cell line, 3T12, did not show any significant difference in treated and untreated animals. In contrast, whereas moderate levels of TNF-alpha were detected in the broncho-alveolar lavage (BAL) fluid supernatants of controls, the NiSO(4) treatment highly suppressed TNF-alpha production with a maximum observed after 2 days. TNF-alpha suppression was found to be transient, at least with the lowest NiSO(4) dose, with levels returning to normal after 7 days. A non-significant increase in IFN-gamma was observed in the BAL fluids of treated animals at each time of examination. Taken together, these results indicate that NK cell activity and TNF-alpha secretion are sensitive targets for instilled NiSO(4) in Wistar rats.

Serum-borne factor(s) of 1,1-dichloroethylene and 1,2-dichlorobenzene-treated mice inhibited in vitro antibody forming cell response and natural killer cell activity.

1,1-Dichloroethylene and 1,2-dichlorobenzene administered to mice produced liver and/or kidney damage which was quantified in this study by a histochemical method. The in vitro effect of sera obtained from these mice on antibody forming cell (AFC) response and natural killer (NK) cell activity was investigated in parallel with the assessment of sera tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. 1,1-Dichloroethylene (100, 150 and 200 mg/kg) provoked liver and kidney damage. Peak kidney damage occurred 16 h after the dose was administered and at 24 h in the case of the liver. During the peak level of liver damage, a serum-borne immunosuppressive effect was also at its highest level. With respect to sera cytokine levels, an increase of TNF-alpha and IL-6 was detected earlier, i.e. 6 h after toxic administration, followed by a decrease that tended toward a baseline level. There was a relationship between the tissue damage induced by 1,1-dichloroethylene and the immunosuppressive effect of mice sera on AFC response and NK cell activity. 1,2-Dichlorobenzene (300, 500 and 600 mg/kg) provoked only liver damage. Peak liver damage severity was observed 48 h after toxic administration, whereas the highest serum-borne immunosuppressive effect was observed almost immediately, i.e. 6 h after administration. As regards sera cytokine levels, only TNF-alpha could be detected 6 h after administering 500 and 600 mg/kg doses of 1,2 dichlorobenzene. There was a relationship between the liver damage induced by 1,2-dichlorobenzene and the immunosuppressive effect of mice sera on the AFC response. In view of the above results, this study suggests that the immunosuppressive effect in sera of mice treated with 1,1-dichloroethylene and 1,2-dichlorobenzene may result from tissue damage, and that the increased levels of TNF-alpha and IL-6 in sera may contribute to this effect. Further studies are needed to clarify the factor(s) responsible, including transforming growth factor-beta1 (TGF-beta1) causing immunosuppression.

TDI inhalation in guinea-pigs involves migration of dendritic cells.

Toluene diisocyanate (TDI) can cause occupational asthma, but the mechanism underlying sensitization to this chemical compound remains controversial. The present study aims to investigate whether tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) liberated in the lungs after TDI inhalation can contribute to the migration of dendritic cells from respiratory airways towards lung associated lymph nodes for presentation of TDI hapten. Exposure was studied in two modes: (1) acute exposure (experiment no. 1, 2 and 3) where animals were exposed to 2.962, 1.060, and 1.076 ppm TDI for 1, 4, and two periods of 4 h, respectively; (2) subacute exposure (experiment no. 4, 5 and 6) where animals were exposed to 0.066, 0.110, and 0.999 ppm TDI for 48 h for the two lower doses and 5 days for the highest dose. Depending on the modes of exposure, two to four post exposure times were selected. After acute exposure to 2.962 ppm TDI for 1 h, the increase in TNF-alpha and IL-6 levels in bronchoalveolar lavage (BAL) fluid was observed immediately at the end of inhalation exposure, whereas the maximum number of dendritic cells and total cells occurred at post exposure times of 48 h and 5 days, respectively. In two other acute exposures, the peak increases in TNF-alpha, IL-6 and total cell numbers were observed at 48 h post exposure time, whereas the peak increase in dendritic cells occurred at 24 h. After subacute exposure to 48 h TDI, where TDI concentrations were relatively low (0.006 or 0.110 ppm), a parallel increase in TNF-alpha and IL-6 levels, dendritic and total cell numbers were observed at 0 h post exposure time. This phenomenon was also apparent at 24 h post exposure time when the animals had been exposed to 1.999 ppm TDI for 5 days. From these results, we can conclude that dendritic cells could play a key role as antigen presenting cells in the development of TDI-induced respiratory sensitization, and that their migration toward lung-associated lymph nodes is probably conditioned by cytokine release in their micro-environment. Future work must delineate whether TNF-alpha and IL-6 are solely responsible for the migration of dendritic cells after TDI inhalation, for example by using antibodies to neutralize these cytokines.

Decreased serum ceruloplasmin concentration in aluminum welders exposed to ozone.

During an epidemiological survey on arc welders, serum copper and ceruloplasmin were determined in two groups of workers. One group consisted of aluminum welders who were divided into two groups: 13 welders working inside aluminum tanks (confined atmosphere) and 8 welders engaged in the production of vans for dump trucks (nonconfined atmosphere). The reference group consisted of 26 workers of the same plant who were not exposed to welding fumes. Ozone, the major pollutant in aluminum arc welding, was thought to be the principal factor in the significant decrease (P less than 0.01) of mean ceruloplasmin in confined welders. This decrease in the level of ceruloplasmin was still within the reference values and was not linked to age or to tobacco consumption. We found a linear relationship between ceruloplasmin concentration and the cumulated worktime along the week. This effect could be a sign in the serum of a lung reaction against oxidant activity in this type occupational exposure.

[Effect of smoking on the concentration and activity of serum alpha-1 anti-protease according to Pi phenotype]. / Effet du tabagisme sur la concentration et l'activité de l'alpha-1 anti-protéase sérique selon le phénotype Pi.

In an epidemiological study on the respiratory pathology of 1 100 iron miners, the alpha 1 protease inhibitor concentration (alpha 1 Pi) and the elastase inhibitory capacity (EIC) of serum were determined in 97 men with deficient Pi phenotype (73 MS, 24 MZ or S) compared with PiM non deficient men adjusted for age and tobacco consumption. There were differences in alpha 1 Pi concentration and in alpha 1 inhibitory capacity between phenotype groups in agreement with the results of other studies. Smoking produces an increase of serum alpha 1 Pi concentration and EIC in all Pi phenotype groups. This increase is more important (30%) in the MS group than in the others (MZ 20%, M 12%). This effect which appears to be related to smoking intensity does not seem to have a link with an alteration or a modification of the molecular function which is at a rate of 70% in all cases.

[Enthesopathy in inflammatory spondyloarthropathy. Incidence, clinical, radiological and anatomical descriptions. Current status of the question. Apropos of 37 cases]. / Les enthésopathies des spondyloarthropathies inflammatoires. Fréquence, description clinique, radiologique et anatomique. Etat actuel de la question. A propos de 37 observations.

Based on a series of 37 personal patients and data from the literature, a number of characteristics of enthesopathies can be observed in the course of inflammatory spondyloarthropathies. Our series is based on 20 cases of ankylosing spondylitis (ASP), 8 cases of Fiessinger-Leroy-Reiter syndrome, 8 cases of psoriatic rheumatism (Pso Rh) and one combined form (psoriasis + Reiter + ASP). As well as the frequent involvement of the calcaneus (29 patients), we found more unusual extra-calcaneal localisations in 23 patients. The clinical symptomatology consisted of pain on activity and on weight-bearing at the sites of insertion of the tendons, which were sometimes swollen. The disease was occasionally very incapacitating. The radiological signs consist of lesions of erosion (initially) and reconstruction (subsequently). The histological signs consist of zones of osseous reorganisation and osteo-tendinous inflammatory infiltration. The mechanism of these enthesopathic lesions is still unclear. Our observations are similar to those reported in the literature, which are essentially paediatric studies. Enthesopathy appears to be a diagnostic and lesional element in common with inflammatory spondyloarthropathies (which include ASP, Reiter's Pso Rh, enteropathic rheumatisms and Behçet's disease) and, at least partially, with juvenile rheumatisms. In the latter case, the precocity of the tendinoperiosteal signs seems to be a very important element in the orientation of the diagnosis at the pre-spondylitic stage.

[Systematic research on enthesopathies in chronic rheumatism. Results and pathological significance. Relation to erosive spondylitis and other tendinous or synovial lesions]. / Recherche systématique des enthésopathies au cours des rhumatismes chroniques. Résultats et signification pathologique. Rapport avec la spondylite érosive et les autres lésions tendineuses ou synoviales.

A routine investigation for rheumatic tendon lesions was conducted in 47 patients with an inflammatory spondylo-arthropathy and in 30 patients with rheumatoid arthritis. The incidence of tendon lesions (calcaneal and extra-calcaneal) differed very significantly (p less than 0.001) between the two groups (58.3% of patients with inflammatory spondylo-arthropathy had at least one tendon lesion, 6.6% of patients with rheumatoid arthritis). These results and data from the literature suggest that rheumatic tendon lesions are a characteristic feature of spondylo-arthropathy in the same way as sacro-iliitis, the absence of subcutaneous nodules, the absence of rheumatoid factor and the high incidence of histocompatibility antigen HLA B27. Together with this diagnostic value, there is also a histopathological value: inflammatory and ossifying tendinitis contrasts with the destructive synovitis of rheumatoid arthritis and can be considered to be a "sign" of inflammatory spondylo-arthropathy. Tendinitis and juxta-articular bone lesions in the limbs, so-called "peripheral" lesions, are similar to the vertebral lesions around the intervertebral disk and the posterior interapophyseal joints found in inflammatory spondylo-arthropathy. These lesions seem to be a common pathological feature, at least in part, with the polyarthropathies of childhood.

[Enthesopathies in ankylosing spondylitis and seronegative inflammatory rheumatism. 28 cases]. / Les enthésopathies dans la spondylarthrite ankylosante et les rhumatismes inflammatoires séronégatifs. 28 observations.

A few demonstrative cases of severe and disabling enthesopathy in patients with ankylosing spondylitis (AS) and related syndromes, psoriatic arthritis (PA) or Reiter's disease (RD) have prompted the authors to investigate the incidence of enthesopathy in such patients. A retrospective clinical and radiological study was conducted in 48 patients (mean age: 34.8 years) 27 of whom had AS, 9 RD and 12 PA. The overall incidence of enthesopathy was 58.3%. Beside the classical calcaneal lesions (50%), extracalcaneal manifestations of the disease involving the knees and shoulders were found in 39% of the patients. The HLA B27 antigen was detected in 87% of patients with enthesopathy, while 82% had clinical inflammation of the spine. The mean duration of clinical symptoms due to enthesopathy was 2-6 weeks in 36% and 6 months to 1 year in 45%. One striking feature of enthesopathy in this series was the lack of response to steroidal and non-steroidal anti-inflammatory drugs contrasting with the response of the associated arthritis. Since enthesopathies appear to be of diagnostic significance in the group of arthropathies of the spine, their incidence in other articular diseases should be the object of systematic comparative evaluations. A diffuse exacerbation of enthesopathy may constitute the initial manifestation of seronegative HLA B27 positive arthropathy, which is not without therapeutic implications.