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The Role of IL-1β in Nicotine-Induced Immunosuppression and Neuroimmune Communication

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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.

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Abbreviations

[Ca2+]i :

intercellular calcium concentration

NT:

nicotine

PTK:

protein tyrosine kinase

HPA:

hypothalamus-pituitary-adrenal

LEW:

Lewis

KO:

knockout

WT:

wild-type

ICV:

intracerebroventricular

aCSF:

artificial cerebrospinal fluid

AFC:

antibody-forming cell

qPCR:

real-time PCR

CORT:

corticosterone

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Acknowledgements

The authors would like to thank Mr. Steve Randock and Ms. Paula Bradley for their help with graphics and editing, respectively.

Disclosures

The authors have no financial conflict of interest.

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Authors and Affiliations

  1. Respiratory Immunology Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr., S.E., Albuquerque, NM, 87108, USA

    Seddigheh Razani-Boroujerdi, Raymond J. Langley, Shashi P. Singh, Juan Carlos Pena-Philippides, Jules Rir-sima-ah, Sravanthi Gundavarapu, Neerad C. Mishra & Mohan L. Sopori

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  1. Seddigheh Razani-Boroujerdi
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  2. Raymond J. Langley
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  3. Shashi P. Singh
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  4. Juan Carlos Pena-Philippides
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  5. Jules Rir-sima-ah
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  6. Sravanthi Gundavarapu
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  7. Neerad C. Mishra
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  8. Mohan L. Sopori
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Corresponding author

Correspondence to Mohan L. Sopori.

Additional information

This work was supported in part by grants from the US Army Medical Research and Material Command (GW093005), the National Institutes of Health (RO1 DA017003), and the Defense Threat Reduction Agency (HDTRA 1-08-C-002)

S. Razani-Boroujerdi and R. Langley contributed equally to the work.

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Razani-Boroujerdi, S., Langley, R.J., Singh, S.P. et al. The Role of IL-1β in Nicotine-Induced Immunosuppression and Neuroimmune Communication. J Neuroimmune Pharmacol 6, 585–596 (2011). https://doi.org/10.1007/s11481-011-9284-5

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  • DOI: https://doi.org/10.1007/s11481-011-9284-5

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