RESUMO
STUDY DESIGN: This study used immunohistochemistry and an enzyme immunoassay to quantify interleukin-1α (IL-1α) and prostaglandin E2 (PGE2) levels in the spinal cord of rats at 1 day after painful cervical facet joint injury. OBJECTIVE: The objective of this study was to determine to what extent spinal inflammation is initiated early after a painful loading-induced injury of the C6-C7 facet joint in a rat model. SUMMARY OF BACKGROUND DATA: A common source of neck pain, the cervical facet joint is susceptible to loading-induced injury, which can lead to persistent pain. IL-1α and PGE2 are associated with joint inflammation and pain, both locally in the joint and centrally in the spinal cord. Joint inflammation has been shown to contribute to pain after facet joint injury. Although spinal neuronal hyperactivity is evident within 1 day of painful facet injury, it is unknown if inflammatory mediators, such as IL-1α and PGE2, are also induced early after painful injury. METHODS: Rats underwent either a painful C6-C7 facet joint distraction or sham procedure. Mechanical sensitivity was assessed, and immunohistochemical and enzyme immunoassay techniques were used to quantify IL-1α and PGE2 expression in the spinal cord at day 1. RESULTS: Both IL-1α and PGE2 were significantly elevated (P≤ 0.04) at day 1 after painful injury. Moreover, although both spinal IL-1α and PGE2 levels were correlated with the withdrawal threshold in response to mechanical stimulation of the forepaw, this correlation was only significant (P = 0.01) for PGE2. CONCLUSION: The increased expression of 2 inflammatory markers in the spinal cord at 1 day after painful joint injury suggests that spinal inflammation may contribute to the initiation of pain after cervical facet joint injury. Further studies will help identify functional roles of both spinal IL-1α and PGE2 in loading-induced joint pain. LEVEL OF EVIDENCE: N/A.
Assuntos
Vértebras Cervicais/lesões , Dinoprostona/biossíntese , Interleucina-1alfa/biossíntese , Mielite/patologia , Dor/patologia , Articulação Zigapofisária/lesões , Animais , Vértebras Cervicais/metabolismo , Dinoprostona/genética , Regulação da Expressão Gênica , Masculino , Mielite/metabolismo , Dor/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Prostaglandina E/biossíntese , Receptores de Prostaglandina E/genética , Medula Espinal/metabolismo , Medula Espinal/patologia , Fatores de TempoRESUMO
BACKGROUND: Exposure to ultraviolet (UV) radiation causes various forms of acute and chronic skin damage, including immunosuppression, inflammation, premature aging and photodamage. Furthermore, it induces the generation of reactive oxygen species, produces proinflammatory cytokines and melanocyte-stimulating hormone (MSH) and increases tyrosinase activity. The aim of this study was to evaluate the potential photoprotective effects of Rheum rhaponticum L. rhizome extract on human UV-stimulated melanocytes. METHODS: The effects of Rheum rhaponticum rhizome extract on tyrosine kinase activity, and on interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α), and α-MSH production in human epidermal melanocytes were evaluated under UV-stimulated and non-stimulated conditions. Antioxidant activity was evaluated by lipid peroxidation and 1,1-dyphenyl-2-picryl-hydrazyl (DPPH) assays, while anti-tyrosinase activity was evaluated by the mushroom tyrosinase method. RESULTS: Rheum rhaponticum L. rhizome extract showed in vitro antioxidant properties against lipid peroxidation, free radical scavenging and anti-tyrosinase activities, and inhibited the production of IL-1α, TNF-α, α-MSH, and tyrosine kinase activity in melanocytes subjected to UV radiation. CONCLUSIONS: These results support the inclusion of Rheum rhaponticum L. rhizome extract into cosmetic, sunscreen and skin care products for the prevention or reduction of photodamage.
Assuntos
Antioxidantes/farmacologia , Citocinas/biossíntese , Melanócitos/efeitos dos fármacos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Rheum , Pele/efeitos dos fármacos , alfa-MSH/biossíntese , Antioxidantes/uso terapêutico , Compostos de Bifenilo/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Sequestradores de Radicais Livres/farmacologia , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1alfa/biossíntese , Peroxidação de Lipídeos/efeitos dos fármacos , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Fitoterapia , Picratos/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Rizoma , Pele/metabolismo , Pele/efeitos da radiação , Dermatopatias/etiologia , Dermatopatias/metabolismo , Dermatopatias/prevenção & controle , Fator de Necrose Tumoral alfa/biossíntese , Raios UltravioletaRESUMO
The reports regarding the mutual influence between the central nervous system and the immune system constitute a vast and somewhat controversial body of literature. Stress is known to disturb homeostasis, impairing immunological functions. In this study, we investigated the hematopoietic response of Chlorella vulgaris (CV)-treated mice exposed to single (SST) and repeated stress (RST). We observed a reduction in the numbers of hematopoietic progenitors (HP) in the bone marrow and long-term bone marrow cultures (LTBMC) using flow cytometry and a coinciding decrease in the number of granulocyte-macrophage colonies (CFU-GM) after treatment with both stressors, but SST caused a more profound suppression. We observed a proportional increase in the colony-stimulating activity (CSA) of the serum of animals subjected to SST or RST. In the bone marrow, SST and RST induced a decrease in both mature myeloid and lymphoid populations but did not affect pluripotent hematopoietic progenitors (Lin(-)Sca-1(+)c-kit(+), LSK), and again, a more profound suppression was observed after SST. We further quantified the levels of interleukin-1α (IL-1α) and interleukin-6 (IL-6) and the number of myeloid cells in LTBMC. Both SST and RST reduced the levels of these cytokines to similar degrees. The myeloid population was also reduced in LTBMC, and SST induced a more intense suppression. Importantly, CV treatment prevented the changes produced by SST and RST in all of the parameters evaluated. Together, our results suggest that CV treatment is an effective tool for the prophylaxis of myelosuppression caused by single or repeated stressors.
Assuntos
Chlorella vulgaris/química , Hematopoese/fisiologia , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/fisiopatologia , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Interleucina-1alfa/biossíntese , Interleucina-6/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Mieloides/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Estresse Psicológico/líquido cefalorraquidianoRESUMO
In this study we demonstrated that the oral administration of ß-1,3-glucan (Imunoglucan®) protects mice from a lethal dose of Listeria monocytogenes (LM) when administered prophylactically for 10 days at the doses of 150 and 300 mg/kg, with survival rates up to 40%. These doses also prevented the myelosuppression and the splenomegaly caused by a sublethal infection with LM, due to increased numbers of granulocyte-macrophage progenitors (CFU-GM) in the bone marrow. Investigation of the production of colony-stimulating factors revealed an increased colony-stimulating activity (CSA) in the serum of infected mice pre-treated with Imunoglucan®. The treatment also restored the reduced ability of stromal cells to display myeloid progenitors in long-term bone marrow cultures (LTBMC) and up-regulated IL-6 and IL-1α production by these cells in the infected mice, which was consistent with higher number of non-adherent cells. Additional studies to investigate the levels of interferon-gamma (INF-γ) in the supernatant of splenocyte cultures demonstrated a further increase in the level of this cytokine in infected-treated mice, compared to infected controls. In all cases, no differences were observed between the responses of the two optimal biologically effective doses. In contrast, no significant changes were produced by the treatment with the 50mg/kg dose. In addition, no changes were observed in normal mice treated with the three doses used. All together our results suggest that orally given Imunoglucan® indirectly modulates immune activity and probably disengages Listeria induced suppression of these responses by inducing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (CSFs, IL-1α, IL-6, and INF-γ).
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Hematopoese/efeitos dos fármacos , Hematopoese/imunologia , Células-Tronco Hematopoéticas/imunologia , Listeriose/prevenção & controle , beta-Glucanas/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Técnicas de Cultura de Células , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Células Progenitoras de Granulócitos e Macrófagos/citologia , Células Progenitoras de Granulócitos e Macrófagos/efeitos dos fármacos , Células Progenitoras de Granulócitos e Macrófagos/imunologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-1alfa/biossíntese , Interleucina-1alfa/imunologia , Interleucina-6/biossíntese , Interleucina-6/imunologia , Listeria monocytogenes/efeitos dos fármacos , Listeriose/complicações , Listeriose/imunologia , Listeriose/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Esplenomegalia/etiologia , Esplenomegalia/imunologia , Esplenomegalia/prevenção & controle , beta-Glucanas/administração & dosagemRESUMO
OBJECTIVE: The objective of this study was to evaluate the effect of a calcium hydroxide Ca(OH)(2)-based paste (Calen) associated or not to 0.4% chlorhexidine digluconate (CHX) on RAW 264.7 macrophage cell line culture. STUDY DESIGN: The cell viability (MTT assay), immunostimulating properties (NO dosage), and anti-inflammatory properties (NO, TNF-alpha, and IL-1alpha dosage) were evaluated after cell exposure to the materials. Data were analyzed statistically by Kruskal-Wallis test at 5% significance level. RESULTS: There was low immunostimulating activity of the Calen paste associated or not to 0.4% CHX in the different materials' concentrations evaluated (P > .05). Anti-inflammatory activity with inhibition of NO and cytokine (TNF-alpha and IL1-alpha) release was observed only with Ca(OH)(2) + CHX at the highest concentration (25 microg/mL). CONCLUSION: As the Calen paste associated to 0.4% CHX did not alter cell viability or the immunostimulating and anti-inflammatory properties, the addition of CHX brought no benefits to the Ca(OH)(2)-based paste with regard to the tested parameters.
Assuntos
Anti-Infecciosos Locais/toxicidade , Hidróxido de Cálcio/toxicidade , Clorexidina/toxicidade , Macrófagos/efeitos dos fármacos , Irrigantes do Canal Radicular/toxicidade , Anti-Infecciosos Locais/farmacologia , Hidróxido de Cálcio/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Clorexidina/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Interleucina-1alfa/biossíntese , Óxido Nítrico/biossíntese , Materiais Restauradores do Canal Radicular/farmacologia , Materiais Restauradores do Canal Radicular/toxicidade , Irrigantes do Canal Radicular/farmacologia , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The ability of culture-filtrate proteins to induce a cellular immune response in infected mice and humans was investigated. A crude extract culture filtrate of Nocardia brasiliensis (CFA) and five semi-purified CFA fractions (P1, P2, P3, P4, P5) were used to stimulate BALB/c mice spleen-cell cultures. The animals were divided into three groups: the first group was infected with 1 x 10(7) CFU of N. brasiliensis in the footpad, the second group was immunized with heat-killed bacteria, and the third was injected with sterile saline. IFN-gamma, IL-1alpha, and IL-4 concentrations were determined in culture supernatants. Protein fractions eliciting IFN-gamma production in mice, as well as the CFA, were used to stimulate IFN-gamma production and in vitro cell proliferation assays with peripheral blood mononuclear cells of patients with actinomycetoma by N. brasiliensis, individuals with pulmonary tuberculosis, and healthy controls. In mice, CFA and three of the protein fractions (P3, P4 and P5) induced significant IFN-gamma production in the infected group. In humans, only the CFA-induced IFN-gamma production and cell proliferation in the group of patients with actinomycetoma. There was no stimulation in tuberculosis patients nor healthy controls. These results suggest that some culture-filtrate antigens are recognized by patients with active actinomycetoma and do not cross-react with M. tuberculosis antigens, being therefore potential candidates to develop a diagnostic test.
Assuntos
Antígenos de Bactérias/imunologia , Micetoma/imunologia , Micetoma/microbiologia , Nocardiose/imunologia , Nocardiose/microbiologia , Nocardia/imunologia , Adolescente , Adulto , Animais , Proliferação de Células , Células Cultivadas , Feminino , Humanos , Interferon gama/biossíntese , Interleucina-1alfa/biossíntese , Interleucina-4/biossíntese , Leucócitos Mononucleares , Linfócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Nocardia/isolamento & purificação , Baço/imunologia , Tuberculose Pulmonar/complicaçõesRESUMO
Protein-energy malnutrition (PEM) modifies resistance to infection, impairing a number of physiological processes, including hematopoiesis. In this study, we examined a few aspects of the inflammatory response to LPS in a model of PEM. We evaluated the cellularity of the blood, bone marrow and spleen, as well as phagocytic, fungicidal and spreading activity, the production in vivo and in vitro of TNF-alpha, IL-1alpha and IL-6, and the expression of CD14 and TLR-4/MD-2 receptors in macrophages. Two-month-old male Swiss mice were submitted to PEM with a low-protein diet containing 4% protein as compared to 20% protein in the control diet. When the experimental group had attained about 20% loss of their original body weight, they were used in the experiments. Malnourished animals presented anemia, leucopenia and severe reduction in bone marrow, spleen and peritoneal cavity cellularity. The production of TNF-alpha, IL-1alpha and IL-6 stimulated in vivo with LPS and the production of IL-6 in bone marrow cells cultured with LPS and the production of TNF-alpha in bone marrow, spleen and peritoneal cells cultured with LPS were significantly lower in malnourished animals. The expression of CD14 and TLR-4/MD-2 receptors was found to be significantly lower in macrophages of malnourished animals. These findings suggest that malnourished animals present a deficient response to LPS. The lower expression of the CD14 and TLR-4/MD-2 receptors may be partly responsible for the immunodeficiency observed in the malnourished mice. These data lead us to infer that the nutritional state interferes with the activation of macrophages and with the capacity to mount an immune response.