Dissection of peripheral and central endogenous opioid modulation of systemic interleukin-1beta responses using c-fos
K M Buller1, A S Hamlin, P B Osborne
1School of Biomedical Sciences, Queensland Brain Institute, University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia. k.buller@uq.edu.au
Abstract:
In opiate addicts or patients receiving morphine treatment, it has been reported that the immune system is often compromised. The mechanisms responsible for the adverse effects of opioids on responses to infection are not clear but it is possible that central and/or peripheral opioid receptors may be important. We have utilised an experimental immune challenge model in rats, the systemic administration of the human pro-inflammatory cytokine interleukin-1beta (IL-1beta) to study the effects of selectively blocking peripheral opioid receptors only (using naloxone methiodide) or after blocking both central and peripheral opioid receptors (using naloxone). Pre-treatment with naloxone methiodide decreased (15%) IL-1beta-induced Fos-immunoreactivity (Fos-IR) in medial parvocellular paraventricular nucleus (mPVN) corticotropin-releasing hormone (CRH) neurons but increased responses in the ventrolateral medulla (VLM) C1 (65%) and nucleus tractus solitarius (NTS) A2 (110%) catecholamine cell groups and area postrema (136%). However no effect of blocking peripheral opioid receptors was detected in the central nucleus of the amygdala (CeA) or dorsal bed nucleus of the stria terminalis (BNST). We next determined the effect of blocking both central and peripheral opioid receptors with naloxone and, when compared to the naloxone methiodide pre-treated group, a further 60% decrease in Fos-IR mPVN CRH neurons induced by IL-1beta was detected, which was attributed to block of central opioid receptors. Similar comparisons also detected decreases in Fos-IR neurons induced by IL-1beta in the VLM A1, VLM C1 and NTS A2 catecholamine cell groups, area postrema, and parabrachial nucleus. In contrast, pre-treatment with naloxone increased Fos-IR neurons in CeA (98%) and dorsal BNST (72%). These results provide novel evidence that endogenous opioids can influence central neural responses to systemic IL-1beta and also suggest that the differential patterns of activation may arise because of actions at central and/or peripheral opioid receptors that might be important in regulating behavioural, hypothalamic-pituitary-adrenal axis and sympathetic nervous system responses during an immune challenge.
Insights
Opioid use can impair immune responses. This study shows blocking peripheral opioid receptors affects brain responses to inflammation, while blocking central receptors alters responses in key brain areas, impacting immune regulation.
Area of Science:
- Neuroimmunology
- Opioid receptor pharmacology
- Cytokine signaling
Background:
- Opioid administration can compromise immune function, but mechanisms are unclear.
- Central and peripheral opioid receptors may mediate these effects.
Purpose of the Study:
- To investigate the role of central and peripheral opioid receptors in neural responses to the pro-inflammatory cytokine interleukin-1 beta (IL-1β).
- To elucidate opioid receptor involvement in immune challenge responses.
Main Methods:
- Utilized an experimental immune challenge model in rats with systemic administration of IL-1β.
- Investigated effects of blocking peripheral opioid receptors (naloxone methiodide) and both central/peripheral receptors (naloxone).
- Measured Fos-immunoreactivity (Fos-IR) in specific brain nuclei to assess neural activation.
Main Results:
- Blocking peripheral opioid receptors altered IL-1β-induced Fos-IR in the paraventricular nucleus, ventrolateral medulla, and nucleus tractus solitarius.
- Blocking both central and peripheral receptors with naloxone further decreased Fos-IR in the paraventricular nucleus and catecholamine cell groups.
- Naloxone, but not naloxone methiodide, increased Fos-IR in the central nucleus of the amygdala and dorsal bed nucleus of the stria terminalis.
Conclusions:
- Endogenous opioids differentially influence central neural activation patterns in response to systemic IL-1β.
- Distinct central and peripheral opioid receptor actions contribute to regulating neuroendocrine and autonomic responses during immune challenges.
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