Early onset periodontitis (EOP) is a chronic inflammatory periodontal disease with a strong genetic link affecting individuals aged 17 to 25. In the familial studies we tested the hypothesis about the role of Th1 and Th2 cytokines in the pathogenesis of EOP disease. The study involved 6 individuals with EOP disease and their 6 siblings with healthy periodontium. Actinobacillus actinomycetemcomitans (A. a.), a bacterium typical for EOP, was detected in all people studied. Th1 and Th2 cytokine production was measured after in vitro stimulation. Peripheral blood mononuclear cells (PBMC) were isolated and cultivated for 24 h and 7 days with PWM, A. a. or Escherichia coli. The levels of IL&#x2013;4, IFN-gamma, IgA, IgG and IgM were measured by ELISA methods. After in vitro stimulation of PBMC, a significantly higher production of IL&#x2013;4 and significantly lower production of IFN-gamma were found in the group of patients compared with their healthy siblings. The increased level of IL&#x2013;4 in patients was in good agreement with an increased level of IgM after stimulation of lymphocytes with E. coli. These results support Seymour&#x2019;s hypothesis according to which patients with progressive disease primarily activate Th2 lymphocytes while non-susceptible individuals activate Th1 lymphocytes.

Ji&#x159;ina B&#xe1;rtov&#xe1;

Zuzana Kr&#xe1;tk&#xe1;-Opatrn&#xe1;

Jarmila Proch&#xe1;zkov&#xe1;

Otakar Krejsa

Jana Du&#x161;kov&#xe1;

Lubor Mrklas

Helena Tlaskalov&#xe1;

Bo&#x17e;ena Cukrowsk&#xe1;

Th1 and Th2 cytokine profile in patients with early onset periodontitis and their healthy siblings

Oxidative stress in the lung is important in the pathogenesis of COPD. Published data indicate that glucocorticoids inhibit blood cells in their capacity to produce reactive oxygen species (ROS). We investigated the effect of Fluticasone propionate (FP) on the ROS production capabilities of pulmonary cells. Bronchoalveolar lavage (BAL) was performed in smoking COPD patients, before and after a six month, placebo-controlled treatment with FP. BAL cells were stimulated with phorbol myristrate acetate (PMA) alone, and together with superoxide dismutase (SOD). From kinetic plots of ferricytochrome-c conversion we calculated the maximal rate of superoxide production: Vmax. We also examined BAL cell subsets and performed correlation analyses on ROS production and relevant clinical determinants. Paired results were obtained from 6 FP- and 9 placebo-treated patients. No significant change of Vmax was found in both patient groups. Also BAL cellularity was unchanged. Correlation analyses showed a significant (inverse) association 
of Vmax with the number of cigarettes smoked per day. We concluded that a potent inhaled glucocorticoid had no effect on the ROS production capability of BAL cells from smoking COPD patients. Apparently, heavy smoking impaired the ability of alveolar macrophages to produce ROS, which was not further decreased by FP.

Gert T. Verhoeven

Annemarie J.M. Wijkhuijs

Herbert Hooijkaas

Henk C. Hoogsteden

Wim Sluiter

Effect of an inhaled glucocorticoid on reactive oxygen species production by bronchoalveolar lavage cells from smoking COPD patients

We investigated morphological alterations induced by s.c. injection of 2.5 &#956;g of Bothrops jararaca venom in rats. Intense disorganisation of collagen fibres was observed 1 min after the venom injection, particularly at regions near vessels and nerves. Mast cells were degranulated, and erythrocytes were seen leaving venules throughout the endothelial junctions. At this time, damaged endothelial cells were not observed. In rats envenomed as above, but immediately after cardiorespiratory failure induced by deep ether anaesthesia, alterations in the connective tissue structures, as previously described, were not observed. The mediation of this haemorrhage was investigated by injecting the venom into the foot pad of mice and compared to the mediation of oedema. Local haemorrhage was significantly reduced in mice pre-treated with capsaicin or guanethidine or submitted to a surgical section of sciatic and saphenous nerves. In these animals, oedema was not affected. Groups treated with methysergide or morphine showed both haemorrhage and oedema significantly reduced. Indomethacin or dexamethasone pre-treatments significantly reduced the oedema, but not the haemorrhage. Moreover, in animals treated with promethazine or mepyramine, oedema and haemorrhage were not affected. These data suggest that local haemorrhage induced by Bothrops jararaca venom is partially controlled by serotonin and neurohumoral mediators. Furthermore, results indicate that haemorrhage and oedema are mediated by different pharmacological systems.

Luis Roberto C. Gon&#231;alves

Mario  Mariano

Local haemorrhage induced by Bothrops jararaca venom: relationship to neurogenic inflammation

Eosinophils are present throughout the airway wall of asthmatics. The nature of the interaction between human airway smooth muscle cells (ASMC) and eosinophils was investigated in this study. We demonstrated, using light microscopy, that freshly isolated eosinophils from healthy donors rapidly attach to ASMC in vitro. Numbers of attached eosinophils were highest at 2 h, falling to 50% of maximum by 20 h. Eosinophil attachment at 2 h was reduced to 72% of control by anti-VCAM-1, and to 74% at 20 h by anti-ICAM-1. Pre-treatment of ASMC for 24 h with TNF-α, 10 nM, significantly increased eosinophil adhesion to 149 and 157% of control after 2 and 20 h. These results provide evidence that eosinophil interactions with ASMC involve VCAM-1 and ICAM-1 and are modulated by TNF-α.

J. Margaret Hughes

Craig A. Arthur

Shane Baracho

Stephen M. Carlin

Kristen M. Hawker

Peter R.A. Johnson

Carol L. Armour

Human eosinophil–airway smooth muscle cell interactions

Fibroblast migration, proliferation, extacellular matrix protein synthesis and degradation are the key events in various biological and pathological processes in pulmonary fibrosis. In addition, biopsy specimens from the lungs of patients with plumomary fibrosis show increased numbers of mast cells which have metachromatic granules containing heparin, histamin and proteases. Little is known about how these products influence pulmonary fibrosis. In the present study, we investigated the effect of heparin and related glycosaminoglycans on PDGF-induced lung fibroblast proliferation and chemotactic response 
in vitro. In addition, we examined the effect of heparin on both the induction of matorix metalloproteinases (MMPs) and MMPs activity in lung fibroblasts in vitro.Heparin, de-N-sulphated heparin but not heparan sulphate inhibited PDGF-induced lung fibroblast proliferation. In contrast, only heparin inhibited PDGF-stimulated human lung fibroblast chemotaxis. Negatively 
charged poly-L-gultamic acid had no effect on either fibroblast proliferation or chemotaxis. Thus the negative charge alone cannot account for the ant-proliferative and anti-chemotactic effects of heparin.Furthermore, heparin and heparan sulphate also had no inhibitory effect on induction of MMPs, including MMP-1 (interstitial collagenase), MMP-2 (gelatinase A) and MMP-9 (gelatinase B). Only heparin inhibited both MMP-1 and MMP-2/MMP-9 activity. Additionally, tissue inhibitor of metalloproteinase type 1 (TIMP-1) and type 2 (TIMP-2) inhibited PDGF-stimulated human lung fibroblast chemotaxis. The ability of heparin to inhibit fibroblast chemotaxis may account for the inhibitory effect of heparin on MMP activity.The above results suggested that heparin and related glycosaminoglycans differentially regulate PDGF-induced lung fibroblast proliferation, chemotaxis and MMPs activity and further that these effects may have a key role in extracellular matrix remodeling in inflammatory lung disease.

Masahiro Sasaki

Masayuki Kashima

Takefumi Ito

Akiko Watanabe

Masaaki Sano

Manabu Kagaya

Takanobu Shioya

Mamoru Miura

Effect of heparin and related glycosaminoglycan on PDGF-induced lung fibroblast proliferation, chemotactic response and matrix metalloproteinases activity

The influence of an anti-allergic agent, suplatast tosilate (IPD-1151T; (±)-[2-[4-(3-ethoxy–2-hydroxypropoxy)phenyl-carbamoyl]-ethyl] dimethylsulfonium p-toluenesulfonate) on allergic bronchoconstriction induced by allergen and methacholine (MCh) were examined in mice. BALB/c mice were sensitized by intraperitoneal injection of dinitrophenylated-keyhole limpet hemocyanin (DNP-KLH) mixed with 
Al(OH)3 (DNP-KLH). IPD-1151T was administered orally once a day for either 5 or 14 days in doses of 10, 30 or 100 mg/kg. Bronchoconstriction was measured 24 h after the final drug administration. IPD-1151T inhibited both antigen- and MCh-mediated bronchoconstriction in actively sensitized mice. The inhibition induced was closely related to the dose and frequency of oral administration of the agent. We also examined the effect of IPD-1151T on IgE production in response to DNP-KLH immunization. IPD-1151T inhibited dose-dependently both total and specific IgE concentrations in serum prepared from mice 15 days after im munization. These results strongly indicate that IPD-1151T inhibits IgE 
production in vivo and results in attenuating effect on bronchoconstriction.

Kazuhito Asano

Tetsuya Mizutani

Toshikazu Shimane

Masataka Hisano

Tadashi Hisamitsu

Harumi Suzaki

The inhibitory effect of anti-allergic agent suplatast tosilate (IPD–1151T) on methacholine- and allergen-induced bronchoconstriction in sensitized mice

The influence of anti-allergic drugs, epinastine hydrochloride (EP) and disodium cromoglycate (DSCG), on the co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with haemocyanin absorbed to aluminium hydroxide were cultured in the presence of 100.0 μg/ml haemocyanin and various concentrations of the agents. Low concentrations (&lt; 1.5 2 10-4 M) of EP and DSCG did not influence spleen cell blastic activity induced by antigenic stimulation, whereas these agents caused significant inhibition of spleen cell activation when 2 × 10-4 M of the agents were added to cell cultures. EP and DSCG also did not affect blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody stimulation even when these cells were cultured in the presence of 2 × 10-4 M of the agents. We next examined the influence of EP and DSCG on the expression of co-stimulatory molecules on spleen cells in response to antigenic stimulation. Sensitized spleen cells were cultured in the presence of 2 × 10-4 M of the agents and the expression of molecules were examined by flow cytometer 24 h later. EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80, but not CD86, on splenic B cells which were enhanced by antigenic stimulation in vitro.

Jun-ichi Ito

Elzbieta Tryka

Ken-ichi Kanai

Sumiko Yamamoto

Suppressive effects of co-stimulatory molecule expressions on mouse splenocytes by anti-allergic agents in vitro

Freek J. Zijlstra

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Mediators of Inflammation publishes papers on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules

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Chief Editor, Professor Agrawal, is an Assistant Clinical Professor of the Division of Basic and Clinical Immunology. Dr. Agrawal's research focuses on the dendritic cells of the immune system in the context of aging and autoimmunity.

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Mediators of Inflammation - Table of contents 2000

title

Mediators of Inflammation publishes papers on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules

Mediators of Inflammation