RESUMO
UNLABELLED: Influence of the novel arthritis drug-substance MCS-18 on the antibody (Ab) production against tetanus toxoid (TT) and diphtheria toxoid (DT) antigens was tested in vivo. Possible involvement of MCS-18 in Toll-like receptor (TLR) signalling pathway was further considered. MATERIALS AND METHODS: Immunization of male CD1 mice was done with subcutaneous injection of TT emulsified in Freund's Complete (FCA) or Incomplete Adjuvant (FIA) and mixed diversly with MCS-18 and different test substances. To investigate the influence of TLR activation Pam3Cys and lipopolysaccharide (LPS) emulsified in FIA were tested in combinations with MCS-18. Antibody production was analysed in vivo by tetanus- or diphtheria-toxin neutralization test. RESULTS: Immunogenicity of TT was significantly enhanced if administered together with FCA or TLR agonists Pam3Cys or LPS emulsified in FIA. It was shown that MCS-18 attenuated strongly the production of anti-TT Ab if administered together with the Ab elicitor FCA or TLR agonists in various combinations. MCS-18 was also active via oral administration. DISCUSSION: These findings suggest that MCS-18 could be a potent, non-toxic antagonist or a down-regulator of TLR signalling pathway. Investigations on further models are needed to establish ifMCS-18 may influence particularly the production of RA-specific auto-antibodies, too.
Assuntos
Formação de Anticorpos/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Receptores Toll-Like/antagonistas & inibidores , Administração Oral , Animais , Anticorpos Antibacterianos/sangue , Toxoide Diftérico/imunologia , Fatores Imunológicos/administração & dosagem , Injeções Subcutâneas , Masculino , Camundongos , Coelhos , Toxoide Tetânico/imunologiaRESUMO
There are many studies demonstrating by different experimental models that non-steroidal antiinflammatory drugs (NSAIDs), also known as cyclooxygenase-2 (COX-2) inhibitors, can modulate immune response such as lymphoid cells differentiation and proliferation. There are experimental data which show that activated B cells can express mRNA COX-2, release prostaglandins (PGs) and produce immunoglobulins in PGs dependent manner. In this study, using different COX-2 inhibitors and applying personalized immunization scheme, we confirmed that it is possible to modulate in vivo antibody response against T cell dependent antigens, substantiating the importance of PGE2 and E prostanoid receptor (EP-R) in antibody generation. Our results point out the fact that we must be more careful when we apply vaccines containing T-cell dependent antigens, such as tetanus or diphteric anatoxin, to the patients under an intense antiinflammatory treatment.
Assuntos
Anticorpos Antibacterianos/biossíntese , Inibidores de Ciclo-Oxigenase 2/farmacologia , Toxina Diftérica/imunologia , Linfócitos T/imunologia , Toxina Tetânica/imunologia , Toxoide Tetânico/imunologia , Animais , Dinoprostona/metabolismo , Toxina Diftérica/metabolismo , Adjuvante de Freund , Imunização Secundária , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Toxina Tetânica/metabolismo , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismoRESUMO
In this paper, we present the effect of the plasma needle on tumor cell surface. The plasma is generated at the tip of a metal needle by using a radio-frequency generator of 13.56 MHz, 100's V amplitude. In our study we investigated the interaction of non-thermal plasma (plasma needle) with living monolayer tumour cells in culture medium. We applied short needle to sample distance (1 mm) at temperature of 25 degrees C, 30 degrees C and 37 degrees C, respectively. Our data sugest that the plasma needle reduces the viability and induces apoptosis of tumour cells. These activities may be very useful in dermatology, where a part of the tissue must be removed with high-precision, without damage to the adjacent cells and without inflammatory reaction.
Assuntos
Apoptose , Gases , Agulhas , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Dermatologia/métodos , HumanosRESUMO
The hydroalcoholic extracts of Calendula officinalis, Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra which exhibited different anti-inflammatory activities were evaluated for the possible mode of action by studying their antioxidant potential. In the present study we investigated if standardized hydroalcoholic extracts of plants such as Calendula officinalis, Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra produced by Hofigal Stock Company could modulate the respiratory burst of human activated neutrophils, as a consequence of their antioxidant capacity. Their antioxidant properties were measured using a colorimetric assay (Total Antioxidant Status kit). We demonstrated that Hypericum perforatum and Calendula officinalis hydroalcoholic extracts possessed a significant antioxidant activity while Plantago lanceolata and Glycyrrhiza glabra hydroalcoholic extracts had a minor antioxidant status. Using reactive oxygen species-generating systems (OZ-activated human PMN neutrophils), Calendula officinalis and Hypericum perforatum extracts showed strong reactive oxygen species scavenging property, Hypericum perforatum extract exhibing the highest scavenging activity. These results confirm the potential of Calendula officinalis and Hypericum perforatum investigated hydroalcoholic extracts as medicinal remedies to be used in different inflammatory/allergic diseases. These extracts could be a useful tool for obtaining new antioxidant/anti-inflammatory agents.
Assuntos
Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Antioxidantes , Calendula , Glycyrrhiza , Humanos , Hypericum , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Plantago , Espécies Reativas de Oxigênio/metabolismoRESUMO
The aim of the present study was to investigate if standardized hydroalcoholic plant extracts such as Calendula officinalis, Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra can suppress in cell-free systems the activities of 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2), key enzymes in the formation of proinflammatory eicosanoids from arachidonic acid (AA). Studies were undertaken to compare the above mentioned plant extracts to a known NSAID (nimesulide) in their ability to inhibit both cyclooxygenase (COX-2) and lipoxygenase (5-LO) activities in cell-free systems. We report on 2 vegetal extracts (Hypericum perforatum and Glycyrrhiza glabra) that inhibit 5-LO activity and 2 vegetal extracts (Plantago lanceolata and Glycyrrhiza glabra) that inhibit COX-2 activity. In this study, we demonstrate for the first time that Glycyrrhiza glabra extract efficiently suppresses both eicosanoids and leukotrienes formation in cell-free systems, implying that this extract directly acts as a dual inhibitor of 5-LO and COX-2 activities. With regard to the properties of dual COX-2/5-LO inhibitors, Glycyrrhiza glabra extract might be a potential drug possessing anti-inflammatory activity devoid of the most troublesome (gastric) side effects seen for drugs used as COX-2 and 5-LO inhibitors. Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra extracts can be added to an already impressive list of these species that have anti-inflammatory activity.