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| Content Provider | Springer Nature Link |
|---|---|
| Author | Razani Boroujerdi, Seddigheh Langley, Raymond J. Singh, Shashi P. Pena Philippides, Juan Carlos Rir sima ah, Jules Gundavarapu, Sravanthi Mishra, Neerad C. Sopori, Mohan L. |
| Copyright Year | 2011 |
| Abstract | Although a number of inflammatory cytokines are increased during sepsis, the clinical trials aimed at down-regulating these mediators have not improved the outcome. These paradoxical results are attributed to loss of the “tolerance” phase that normally follows the proinflammatory response. Chronic nicotine (NT) suppresses both adaptive and innate immune responses, and the effects are partly mediated by the nicotinic acetylcholine receptors in the brain; however, the mechanism of neuroimmune communication is not clear. Here, we present evidence that, in rats and mice, NT initially increases IL-1β in the brain, but the expression is downregulated within 1–2 week of chronic exposure, and the animals become resistant to proinflammatory/pyrogenic stimuli. To examine the relationship between NT, IL-1β, and immunosuppression, we hypothesized that NT induces IL-1β in the brain, and its constant presence produces immunological “tolerance”. Indeed, unlike wild-type C57BL/6 mice, chronic NT failed to induce immunosuppression or downregulation of IL-1β expression in IL-1β-receptor knockout mice. Moreover, while acute intracerebroventricular administration of IL-1β in Lewis (LEW) rats activated Fyn and protein tyrosine kinase activities in the spleen, chronic administration of low levels of IL-1β progressively diminished the pyrogenic and T cell proliferative responses of treated animals. Thus, IL-1β may play a critical role in the perception of inflammation by the CNS and the induction of an immunologic “tolerant” state. Moreover, the immunosuppressive effects of NT might be at least partly mediated through its effects on the brain IL-1β. This represents a novel mechanism for neuroimmune communication. |
| Starting Page | 585 |
| Ending Page | 596 |
| Page Count | 12 |
| File Format | |
| ISSN | 15571890 |
| Journal | Journal of Neuroimmune Pharmacology |
| Volume Number | 6 |
| Issue Number | 4 |
| e-ISSN | 15571904 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2011-06-14 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Nicotine IL-1β Immunosuppression Neuroimmune communication Fyn Virology Neurosciences Immunology Cell Biology Pharmacology/Toxicology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Allergy Pharmacology Immunology |
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