IL-1beta immunoreactive neurons in the human hypothalamus: reduced numbers in multiple sclerosis.
Corticotropin-releasing hormone (CRH)-containing neurons in the paraventricular nucleus (PVN) in the hypothalamus of multiple sclerosis (MS) patients are hyperactivated. Since interleukin-1 (IL-1)beta is a powerful activator of CRH neurons, its immunohistochemical expression was studied in the postmortem hypothalamus of MS patients (n=11) and matched controls (n=11). Hypothalamic tissue of 10/11 MS patients showed demyelinating lesions that in many cases contained IL-1beta-immunoreactive (ir) macrophages and glial cells. In control subjects IL-1beta-ir was only sporadically found in glial cells. Interestingly, abundant IL-1beta-ir was also present in hypothalamic neurons. Neuronal IL-1beta co-localised with oxytocin and not with vasopressin or CRH. IL-1beta clearly yielded a less intense staining in neurons and numbers of IL-1-ir neurons in the PVN were 4.5-fold reduced in MS. We suggest that IL-1beta produced by activated glial cells in the hypothalamus of MS patients may contribute to the activation of the hypothalamic CRH neurons, while reduced expression of neuronal IL-1beta in MS patients may have consequences for neuroendocrine, behavioural or autonomic functioning.
Huitinga
I
I
Graduate School of Neurosciences Amsterdam, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ, Amsterdam, The Netherlands. i.huitinga@nih.knaw.nl
van der Cammen
M
M
Salm
L
L
Erkut
Z
Z
van Dam
A
A
Tilders
F
F
Swaab
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D009412:Nerve Fibers / Q000378:metabolism; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D012016:Reference Values
D007375:Interleukin-1