"Capsaicin, the pungent principle of hot peppers, is a neurotoxin that depletes primary sensory neurons of neuropeptides like tachykinin. The objectives of these experiment was to examine the effects of capsaicin on Salmonel/a typhimurium-induced production of cytokines such as TNF-a, IL-1B, IL-6, IL-10 and IL-12 and on production of nitric oxide in peritoneal macrophages. In addition, the effects of capsaicin on survival rates of S. typhimurium-infected mice and on nuclear transcription factor (NF-kB) activation were also investigated. Mice were pretreated with a single s.c. injection of 100 ug of capsaicin and were infected i.v. with S. typhimurium (5xO5/mouse) in 0.2 ml volume after capsaicin pretreatment. The serum cytokine levels were measured 30, 60, 120, 180 and 240 min after Salmonella infection, using ELISA kits. The activation of NF-B was also examined by gel shift assay in spleens, thymuses and brains of mice that had been pretreated with a single s.c. injection of 100 ug of capsaicin. It was found that Sa/mone/la infection induced the production of TNF-a, IL-1B, IL-6, IL-10 and IL-12, but capsaicin pretreatment inhibited the production of TNF-a, IL-1B, IL-10 and IL-12, but enhanced IL-6 production 120 min after Salmonella infection. Interestingly, the capsaicin pretreatment inhibited the activation of NF-kB in spleens and thymuses. There were no differences in the numbers of bacteria in livers, brains, spleens, kidneys and lungs between capsaicin- pretreated mice and the control animals in applied experimental conditions. Suprisingly, however, capsaicin pretreatment increased both the survival rates of Sa/mone//a-infected mice and production of nitric oxide by peritoneal macrophages compared with capsaicin-untreated control mice. Taken together, these results indicate that the capsaicin-sensitive primary sensory neurons may play an important modulatory role in the production of cytokine, nitric oxide and NF-B activation and the pathogenesis of salmonellosis."
Animals ; Bacteria ; Brain ; Capsaicin* ; Cytokines* ; Enzyme-Linked Immunosorbent Assay ; Interleukin-10 ; Interleukin-12 ; Interleukin-6 ; Kidney ; Liver ; Lung ; Macrophages, Peritoneal ; Mice ; Neuropeptides ; NF-kappa B* ; Nitric Oxide* ; Salmonella Infections* ; Salmonella typhimurium ; Salmonella* ; Sensory Receptor Cells ; Spleen ; Survival Rate ; Tachykinins ; Thymus Gland ; Transcription Factors

No abstract available.
Anaphylaxis* ; Animals ; Hypersensitivity* ; Immunoglobulin E* ; Interferons* ; Mice*

The ultraviolet radiation (UVR) is known to be a potent modulator of many host immune functions and the exposure of experimental animals to the inflammatory effects of UVR induces depressions in their ability to initiate and effectuate various types of cellular immune responses. In this study, the effects of UV-B (280 320 nm) radiation on resistance to a facultative intracellular bacterium, Listeria monocytogenes (LM), were examined at the cellular level. The numbers of cultivable LM recovered from the spleens of UV-B-irradiated mice were decreased at 2 days postinfection compared with those of untreated control mice. However, the acquired immunity, developed 7 days after immunization with streptomycin (SM)-sensitive LM, in either UV-irradiated, LPS- or IL-1-pretreated mice was less stronger than that developed in untreated, control mice. To elucidate the possible mechanisms underlying the observation that UVR did increase innate immunity but decreased acquired immunity of mice to the infection with LM, the effects of UVR of mice on the production of IFN-r by activated splenocytes and TNF-a by peritoneal macrophages were assessed. Activated splenocytes from UV-irradiated mice exhibited a reduced capacity to produce IFN-r and cultured peritoneal macrophages produced more TNF-a in the presence of LPS during 24 hours after UV radiation. Though TNF-r activity was not detected in the sera of LM-infected mice, intravenous LPS injection induced TNF-r production and UVR decreased TNF activity in sera obtained from LM-infected mice with LPS induction 9 days after irradiation. Although Ia-negative macrophages were predominant in the peritoneal macrophages from untreated control mice, the infection of mice with LM caused a marked increase in Ia expression on peritoneal macrophages. However, UVR resulted in decreased expression of Ia molecule on the peritoneal macrophages during the LM infection. These findings suggest that the dual effects of UVR on the innate and acquired immunity of mice to the LM infection may be associated with altered capacities of splenocytes and peritoneal macrophages of the mice to produce cytokines, in addition to decrease of la molecule expression on the macrophages.
Adaptive Immunity ; Animals ; Cytokines ; Depression ; Immunity, Cellular ; Immunity, Innate ; Immunization ; Listeria monocytogenes* ; Listeria* ; Macrophages ; Macrophages, Peritoneal ; Mice* ; Spleen ; Streptomycin ; Tumor Necrosis Factor-alpha*

No abstract available.
Anaphylaxis* ; Animals ; Antibodies, Monoclonal* ; Hypersensitivity* ; Immunoglobulin G* ; Interferons* ; Mice*

BACKGROUND: Platelet-activating factor (PAF) induces nuclear factor (NF)-kappaB activation and angiogenesis and increases tumor growth and pulmonary tumor metastasis in vivo. The role of NF-kappaB activation in PAF-induced angiogenesis in a mouse model of Matrigel implantation, and in PAF-mediated pulmonary tumor metastasis were investigated. METHODS: Angiogenesis using Matrigel and experimental pulmonary tumor metastasis were tested in a mouse model. Electrophoretic mobility shift assay was done for the assessment of NF-kappaB translocation to the nucleus. Expression of angiogenic factors, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were tested by RT-PCR and ELISA. RESULTS: PAF induced a dose- and time-dependent angiogenic response. PAF-induced angiogenesis was significantly blocked by PAF antagonist, CV6209, and inhibitors of NF-kappaB expression or action, including antisense oligonucleotides to p65 subunit of NF-kappaB (p65 AS) and antioxidants such as alpha-tocopherol and N-acetyl-L-cysteine. In vitro, PAF activated the transcription factor, NF-kappaB and induced mRNA expression of TNF-alpha, IL-1alpha, bFGF, VEGF, and its receptor, KDR. The PAF-induced expression of the above mentioned factors was inhibited by p65 AS or antioxidants. Also, protein synthesis of VEGF was increased by PAF and inhibited by p65 AS or antioxidants. The angiogenic effect of PAF was blocked when anti-VEGF antibodies was treated or antibodies against TNF-alpha, IL-1alpha, and bFGF was co-administrated, but not by antibodies against TNF-alpha, IL-1alpha, and bFGF each alone. PAF-augmented pulmonary tumor metastasis was inhibited by p65 AS or antioxidants. CONCLUSION: These data indicate that PAF increases angiogenesis and pulmonary tumor metastasis through NF-kappaB activation and expression of NF-kappaB-dependent angiogenic factors.
Acetylcysteine ; alpha-Tocopherol ; Angiogenesis Inducing Agents ; Animals ; Antibodies ; Antioxidants ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Fibroblast Growth Factor 2 ; Interleukins ; Mice ; Neoplasm Metastasis* ; NF-kappa B ; Oligonucleotides, Antisense ; RNA, Messenger ; Transcription Factors ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A

It is well known that tumor necrosis factor (TNF-a), interleukin-1, platelet-activating factor (PAF) and arachidonic acid metabolites, such as thromboxane and leukotriens, are major mediators involved in the pathogenesis of endotoxic shock. In this study, we have investigated the effect of pentoxifylline (inhibitor of TNF-a release), BN50739 (PAF antagonist), indomethacin (cyclooxygenase inhibitor) and diethylcarbamazine (lipoxygenase inhibitor) on LPS- induced lethality as well as the relationship between major mediators in endotoxic shock. All inhibitors described above except diethylcarbamazine significantly protected mice against LPS- induced lethality. BN50739 and indomethacin were also effective in protection of TNF-a-induced lethality. The elevation of circulating TNF-a by LPS was significantly blocked by BN50739, but not affected by indomethacin. Convulsion appeared shortly after LPS injection was prevented by BN50739 but not by indomethacin, whereas diarrhea and limited movement was prevented by indomethacin but not by BN50739. These results indicate that i) TNF-a, PAF and cyclooxygenase products are important mediators involved in the pathogenesis of septic shock and ii) TNF-a directly influenced the release or production of PAF as well as cyclooxygenase products, and strongly suggest that i) TNF-a and PAF stimulate the release of each other via positive feedback network but TNF-a and cyclooxygenase products do not form the network and ii) PAF and cyclooxygenase product appear not to affect the release of each other.
Animals ; Arachidonic Acid ; Diarrhea ; Diethylcarbamazine ; Gene Expression* ; Indomethacin ; Interleukin-1 ; Mice ; Pentoxifylline ; Prostaglandin-Endoperoxide Synthases ; Seizures ; Shock, Septic ; Tumor Necrosis Factor-alpha*