scholarly journals Immunosuppressive and Anti-Inflammatory Effects of Nicotine Administered by Patch in an Animal Model

2004 ◽  
Vol 11 (3) ◽  
pp. 563-568 ◽  
Author(s):  
Roma Kalra ◽  
Shashi P. Singh ◽  
Juan C. Pena-Philippides ◽  
Raymond J. Langley ◽  
Seddigheh Razani-Boroujerdi ◽  
...  
Keyword(s):  
Animal Model ◽  
Immune System ◽  
Inflammatory Responses ◽  
Nicotine Patch ◽  
Subcutaneous Administration ◽  
Spleen Cells ◽  
Self Administration ◽  
Nicotine Administration ◽  
Nicotine Patches ◽  
Immunological Effects

ABSTRACT To study the immunological effects of nicotine, there are several rodent models for chronic nicotine administration. These models include subcutaneously implanted miniosmotic pumps, nicotine-spiked drinking water, and self-administration via jugular cannulae. Administration of nicotine via these routes affects the immune system. Smokers frequently use nicotine patches to quit smoking, and the immunological effects of nicotine patches are largely unknown. To determine whether the nicotine patch affects the immune system, nicotine patches were affixed daily onto the backs of Lewis rats for 3 to 4 weeks. The patches efficiently raised the levels of nicotine and cotinine in serum and strongly inhibited the antibody-forming cell response of spleen cells to sheep red blood cells. The nicotine patch also suppressed the concanavalin A-induced T-cell proliferation and mobilization of intracellular Ca2+ by spleen cells, as well as the fever response of animals to subcutaneous administration of turpentine. Moreover, immunosuppression was associated with chronic activation of protein tyrosine kinase and phospholipase C-γ1 activities. Thus, in this animal model of nicotine administration, the nicotine patch efficiently raises the levels of nicotine and cotinine in serum and impairs both the immune and inflammatory responses.

scholarly journals Differential Effects of Nicotine and Nicotine Withdrawal on Fear Conditioning in Male Rats

2020 ◽  
Vol 23 (7) ◽  
pp. 469-479 ◽  
Author(s):  
Mykel A Robble ◽  
Isaiah L Holloway ◽  
Elysia Ridener ◽  
Chelsea J Webber ◽  
S Barak Caine ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Nicotine Patch ◽  
Conditioned Fear ◽  
Acoustic Startle ◽  
Subcutaneous Administration ◽  
Nicotine Withdrawal ◽  
Male Rats ◽  
Nicotine Exposure ◽  
Self Administration ◽  
Aversive Events

Abstract Background Tobacco use is prevalent in individuals who are routinely exposed to stress. However, little is known about how nicotine affects responses to trauma. We examined in rats how nicotine exposure affects fear conditioning, a procedure often used to study stress-related psychiatric illness. Methods We examined 2 methods of nicotine exposure: self-administration, modeling voluntary use, and experimenter-programmed subcutaneous administration, modeling medicinal administration (nicotine patch). For self-administered nicotine, rats trained to self-administer nicotine i.v. were fear conditioned (via light cue preceding foot-shock) either immediately after a 12-hour self-administration session or 12 hours later during a period with somatic signs of nicotine withdrawal. For experimenter-delivered nicotine, rats were conditioned after 1–21 days of nicotine delivered by programmable (12 hours on) subcutaneous mini-pumps. Tests to evaluate acoustic startle responses to the conditioning environment (context-potentiated startle) and in the presence or absence of the light cue (fear-potentiated startle) occurred after a 10-day period. Results Rats fear conditioned immediately after nicotine self-administration showed reduced responses to the shock-associated context, whereas those trained during nicotine withdrawal showed exaggerated responses. Experimenter-programmed nicotine produced effects qualitatively similar to those seen with self-administered nicotine. Conclusions Self-administration or experimenter-programmed delivery of nicotine immediately before exposure to aversive events can reduce conditioned fear responses. In contrast, exposure to aversive events during nicotine withdrawal exacerbates fear responses. These studies raise the possibility of developing safe and effective methods to deliver nicotine or related drugs to mitigate the effects of stress while also highlighting the importance of preventing withdrawal in nicotine-dependent individuals.

Pre-quit nicotine decreases nicotine self-administration and attenuates cue- and drug-induced reinstatement

2019 ◽  
Vol 33 (3) ◽  
pp. 364-371
Author(s):  
Kelly J Clemens ◽  
Angela Stuart ◽  
Stuart G Ferguson
Keyword(s):  
Animal Model ◽  
Low Dose ◽  
Drug Effect ◽  
Drug Effects ◽  
Smoking Behaviour ◽  
Self Administration ◽  
Drug Induced ◽  
Nicotine Replacement ◽  
Nicotine Administration ◽  
Mini Pump

Background: Administration of smoking cessation medications in anticipation of a nominated quit date can promote abstinence. How this occurs is not widely understood, but may be due to the disruption of contingencies between smoking behaviour and acute drug effects. Aims: The aim of this study was to explore this relationship, we examined the effect of pre-quit nicotine replacement therapy on susceptibility to relapse in an animal model of nicotine dependence. Methods: Rats were trained to intravenously self-administer nicotine across 20 days. Continuous low-dose nicotine was administered via a mini-osmotic pump either across the last 7 days of self-administration and across 6 days of extinction, or across extinction only. Cue- and drug-induced reinstatements of responding were then measured with mini-pumps retained, the day after mini-pump removal or one week later. Results: Pre-quit nicotine administration markedly reduced self-administration across the last days of training as the response, and its associated cues, no longer reliably predicted an acute drug effect. Pre-quit, but not post-quit, nicotine administration significantly attenuated cue-induced reinstatement once mini-pumps were removed, indicating that the contingency disruption across training reduced the conditioned reinforcing properties of the cue at test. Both pre-quit and post-quit nicotine attenuated nicotine-primed reinstatement. Conclusions: Together these results suggest that administration of a nicotine replacement prior to a nominated quit date may enhance resistance to relapse via disruption of the contingency between a response, its associated cues, and a rewarding nicotine effect.

scholarly journals Ectromelia virus: the causative agent of mousepox

2005 ◽  
Vol 86 (10) ◽  
pp. 2645-2659 ◽  
Author(s):  
David J. Esteban ◽  
R. Mark L. Buller
Keyword(s):  
Immune Response ◽  
Animal Model ◽  
Immune System ◽  
Causative Agent ◽  
Inflammatory Responses ◽  
Variola Virus ◽  
Ectromelia Virus ◽  
Vaccine Testing ◽  
Cellular Components ◽  
Recent Sequencing

Ectromelia virus (ECTV) is an orthopoxvirus whose natural host is the mouse; it is related closely to Variola virus, the causative agent of smallpox, and Monkeypox virus, the cause of an emerging zoonosis. The recent sequencing of its genome, along with an effective animal model, makes ECTV an attractive model for the study of poxvirus pathogenesis, antiviral and vaccine testing and viral immune and inflammatory responses. This review discusses the pathogenesis of mousepox, modulation of the immune response by the virus and the cytokine and cellular components of the skin and systemic immune system that are critical to recovery from infection.

scholarly journals Gastric Microenvironment—A Partnership between Innate Immunity and Gastric Microbiota Tricks Helicobacter pylori

2021 ◽  
Vol 10 (15) ◽  
pp. 3258
Author(s):  
Cristina Oana Mărginean ◽  
Lorena Elena Meliț ◽  
Maria Oana Săsăran
Keyword(s):  
Helicobacter Pylori ◽  
Immune System ◽  
Pathogenic Bacteria ◽  
T Regulatory Cells ◽  
Inflammatory Responses ◽  
Mucosal Barrier ◽  
Pathogen Recognition ◽  
Microenvironmental Factors ◽  
H Pylori ◽  
Major Factors

Helicobacter pylori (H. pylori) carcinogenicity depends on three major factors: bacterial virulence constituents, environmental factors and host’s genetic susceptibility. The relationship between microenvironmental factors and H. pylori virulence factors are incontestable. H. pylori infection has a major impact on both gastric and colonic microbiota. The presence of non-H. pylori bacteria within the gastric ecosystem is particularly important since they might persistently act as an antigenic stimulus or establish a partnership with H. pylori in order to augment the subsequent inflammatory responses. The gastric ecosystem, i.e., microbiota composition in children with H. pylori infection is dominated by Streptoccocus, Neisseria, Rothia and Staphylococcus. The impairment of this ecosystem enhances growth and invasion of different pathogenic bacteria, further impairing the balance between the immune system and mucosal barrier. Moreover, altered microbiota due to H. pylori infection is involved in increasing the gastric T regulatory cells response in children. Since gastric homeostasis is defined by the partnership between commensal bacteria and host’s immune system, this review is focused on how pathogen recognition through toll-like receptors (TLRs—an essential class of pathogen recognition receptors—PRRs) on the surface of macrophages and dendritic cells impact the immune response in the setting of H. pylori infection. Further studies are required for delineate precise role of bacterial community features and of immune system components.

scholarly journals Inflammatory responses of C57BL/6NKorl mice to dextran sulfate sodium-induced colitis: comparison between three C57BL/6 N sub-strains

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Sou Hyun Kim ◽  
Doyoung Kwon ◽  
Seung Won Son ◽  
Tae Bin Jeong ◽  
Seunghyun Lee ◽  
...  
Keyword(s):  
Animal Model ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Inflammatory Responses ◽  
Inbred Mouse ◽  
Clinical Signs ◽  
Safety Evaluation ◽  
Inbred Mouse Strain ◽  
Drug Safety Evaluation ◽  
Factor Α

Abstract Background Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitis-related clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

scholarly journals Effects of omega-3 supplementation on interleukin and neurotrophin levels in an animal model of schizophrenia

2015 ◽  
Vol 87 (2 suppl) ◽  
pp. 1475-1486 ◽  
Author(s):  
ALEXANDRA I. ZUGNO ◽  
LARA CANEVER ◽  
GUSTAVO MASTELLA ◽  
ALEXANDRA S. HEYLMANN ◽  
MARIANA B. OLIVEIRA ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Animal Model ◽  
Prefrontal Cortex ◽  
Immune System ◽  
Mechanism Of Action ◽  
Neurotrophic Factor ◽  
Concomitant Treatment ◽  
Omega 3 ◽  
Preventive Effect

ABSTRACTNew studies suggest that polyunsaturated fatty acids, such as omega-3, may reduce the symptoms of schizophrenia. The present study evaluated the preventive effect of omega-3 on interleukines (IL) and neurotrophin brain-derived neurotrophic factor (BDNF) levels in the brains of young rats subjected to a model of schizophrenia. Treatment was performed over 21 days, starting on the 30th day of rat's life. After 14 days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25 mg/kg) was started and maintained until the last day of the experiment. BDNF levels in the rat's prefrontal cortex were decreased at 1 h and 24 h after the last administration of ketamine, whereas the group administered with ketamine and omega-3 showed a decrease in BDNF levels only after 24 h. In contrast, both interventions induced similar responses in levels of IL-1β and IL6. These findings suggest that the similarity of IL-1β and IL6 levels in our experimental groups is due to the mechanism of action of ketamine on the immune system. More studies have to be carried out to explain this pathology. In conclusion, according to previous studies and considering the current study, we could suggest a prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia.

scholarly journals Mice with a humanized immune system are resilient to transplantation of human microbiota

2021 ◽  
Author(s):  
Wei Zhou ◽  
Kin-hoe Chow ◽  
Rory Geyer ◽  
Paola Peshkepija ◽  
Elizabeth Fleming ◽  
...  
Keyword(s):  
Animal Model ◽  
Immune System ◽  
Mouse Model ◽  
Fecal Microbiota Transplantation ◽  
Host Immune System ◽  
Donor Strain ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Human Leukocytes ◽  
Human Specific

Human gut microbiota has co-evolved with human, and plays important roles in regulating the development and functioning of the host immune system. To study the human-specific microbiome-immunune interaction in an animal model is challenging as the animal model needs to capture both the human-specific immune functions and the human-specific microbiome composition. Here we combined two widely-used humanization procedures to generate a humanized mouse model (HMA-huCD34) with functional human leukocytes developed from engrafted huCD34+ cells and human fecal microbes introduced through fecal microbiota transplantation, and investigated how the two introduced human components interact. We found that the engrafted human leukocytes are resilient to the transplanted human microbes, while reciprocally the transplanted microbial community in the huCD34 mice was significantly different from mice without a humanized immune system. By tracking the colonization of human fecal Bacteroides strains in the mouse gut, we found that the composition of the strain population changes over time, the trajectory of which depends upon the type of mouse. On the other hand, different from Bacteroides, Akkermansia muciniphila exhibited consistent and rapid fixation of a single donor strain in all tested mice, suggesting strong purifying selection common to all mouse types. Our prospect study illustrated the complex interactions between the transplanted microbiome and different host factors, and suggested that the humanized mouse model may not faithfully reproduce the human-specific microbiome-immune interaction.

scholarly journals Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2 specific CD8 T cell responses following COVID-19

2021 ◽  
Author(s):  
Anna H.E. Roukens ◽  
Marion König ◽  
Tim Dalebout ◽  
Tamar Tak ◽  
Shohreh Azimi ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Nasal Mucosa ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Upper Airway ◽  
Effector Memory ◽  
Long Term Effects ◽  
Activated T Cells

AbstractThe immune system plays a major role in Coronavirus Disease 2019 (COVID-19) pathogenesis, viral clearance and protection against re-infection. Immune cell dynamics during COVID-19 have been extensively documented in peripheral blood, but remain elusive in the respiratory tract. We performed minimally-invasive nasal curettage and mass cytometry to characterize nasal immune cells of COVID-19 patients during and 5-6 weeks after hospitalization. Contrary to observations in blood, no general T cell depletion at the nasal mucosa could be detected. Instead, we observed increased numbers of nasal granulocytes, monocytes, CD11c+ NK cells and exhausted CD4+ T effector memory cells during acute COVID-19 compared to age-matched healthy controls. These pro-inflammatory responses were found associated with viral load, while neutrophils also negatively correlated with oxygen saturation levels. Cell numbers mostly normalized following convalescence, except for persisting CD127+ granulocytes and activated T cells, including CD38+ CD8+ tissue-resident memory T cells. Moreover, we identified SARS-CoV-2 specific CD8+ T cells in the nasal mucosa in convalescent patients. Thus, COVID-19 has both transient and long-term effects on the immune system in the upper airway.

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