Failure of alpha-melanocyte stimulating hormone to attenuate cerebral complications in experimental pneumococcal meningitis.
Alpha-melanocyte-stimulating hormone (alpha-MSH) is an endogenous neuroimmunomodulatory peptide that can inhibit a broad range of inflammatory mediators known to be involved in the pathophysiology of bacterial meningitis. We evaluated the effect of alpha-MSH in a rat model of pneumococcal meningitis. Rats were intracisternally infected with Streptococcus pneumoniae and treatment was started 6 h after infection. Both systemic and intracisternal alpha-MSH failed to influence blood-brain barrier disruption, increased intracranial pressure, brain cytokine concentrations (IL-1beta, IL-6, TNF-alpha, MIP-2, and IL-10), CSF bacterial titers, and clinical parameters of disease severity (weight loss, body temperature, and blood pressure), although the treatment strongly increased the CNS concentrations of alpha-MSH. However, systemic but not intracisternal alpha-MSH slightly reduced the CNS leukocyte accumulation, indicating that leukocyte extravasation is inhibited by alpha-MSH from the blood side. Our results show that alpha-MSH reduces the CNS leukocyte accumulation by its systemic action, but does not attenuate meningitis-associated intracranial complications.
Kastenbauer
S
S
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University of Munich, Marchioninistrasse 15, 81377, Munchen, Germany.
Koedel
U
U
Brzoska
T
T
Luger
T A
TA
Pfister
H W
HW
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001927:Brain Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D002490:Central Nervous System / Q000473:pathology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007958:Leukocyte Count; D008297:Male; D008586:Meningitis, Pneumococcal / Q000150:complications* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017211:Treatment Failure; D000521:alpha-MSH / Q000627:therapeutic use*
D000521:alpha-MSH