PMID- 9730683
OWN - NLM
STAT- MEDLINE
DCOM- 19981103
LR  - 20180213
IS  - 1021-7401 (Print)
IS  - 1021-7401 (Linking)
VI  - 5
IP  - 3-4
DP  - 1998 May-Aug
TI  - Neuroimmunomodulatory actions of hypothalamic interferon-alpha.
PG  - 172-7
AB  - Recent studies have revealed that the brain produces interferon-alpha (IFN-alpha) 
      in response to noninflammatory as well as inflammatory stress and that it might 
      have a role in normal physiology. When administered intracerebrally, IFN-alpha 
      causes diverse effects including fever, anorexia, analgesia and changes in the 
      central neuronal activities. These responses are inhibited by the opioid receptor 
      antagonist naloxone. This is consistent with the reports suggesting that 
      recombinant human (rh) IFN-alpha binds to opioid receptors in rodent brain 
      membrane. We revealed that rhIFN-alpha altered the activity of thermosensitive 
      neurons in the medial preoptic area (MPO) and glucose-responsive neurons in the 
      ventromedial hypothalamus in an opioid-receptor-dependent way. As a stress which 
      produces opioid-dependent analgesia is known to suppress the cytotoxicity of 
      splenic natural killer cells, we investigated whether the administration of 
      beta-endorphin and rhIFN-alpha may induce a similar immunosuppression. We found 
      that central, but not peripheral, injection of both compounds inhibited natural 
      killer (NK) cytotoxicity. Further studies revealed that rhIFN-alpha decreased the 
      activity of MPO neurons via opioid receptors and the altered activity of MPO 
      neurons in turn resulted in the activation of corticotropin-releasing factor 
      neurons, thereby suppressing NK cytotoxicity predominantly through activation of 
      the splenic sympathetic nerve and beta-receptor mechanisms in splenocytes. Thus, 
      IFN-alpha may alter the brain activity to exert a feedback effect on the immune 
      system. Further detailed whole-cell clamping analyses on neuronal mechanisms in 
      rat brain tissue slices showed that the inhibitory effect of rhIFN-alpha on 
      N-methyl-D-aspartate-induced membrane current responses of MPO neurons was 
      mediated not only by opioid receptors but also by the local production of 
      reactive oxygen intermediates, nitric oxide and prostanoids, possibly due to 
      neuron-glial cell interaction.
FAU - Hori, T
AU  - Hori T
AD  - Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka, Japan. 
      thori@physiol.med.kyushu-u.ac.jp
FAU - Katafuchi, T
AU  - Katafuchi T
FAU - Take, S
AU  - Take S
FAU - Shimizu, N
AU  - Shimizu N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Switzerland
TA  - Neuroimmunomodulation
JT  - Neuroimmunomodulation
JID - 9422763
RN  - 0 (Interferon-alpha)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Hypothalamus/*immunology
MH  - Interferon-alpha/*immunology
MH  - Neuroimmunomodulation/*immunology
RF  - 63
EDAT- 1998/09/08 02:04
MHDA- 2000/08/16 11:00
CRDT- 1998/09/08 02:04
PHST- 1998/09/08 02:04 [pubmed]
PHST- 2000/08/16 11:00 [medline]
PHST- 1998/09/08 02:04 [entrez]
AID - nim05172 [pii]
AID - 10.1159/000026334 [doi]
PST - ppublish
SO  - Neuroimmunomodulation. 1998 May-Aug;5(3-4):172-7. doi: 10.1159/000026334.