Failure of alpha-melanocyte stimulating hormone to attenuate cerebral complications in experimental pneumococcal meningitis

Abstract

Alpha-melanocyte-stimulating hormone (α-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 α-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 α-MSH failed to influence blood–brain barrier disruption, increased intracranial pressure, brain cytokine concentrations (IL-1β, IL-6, TNF-α, 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 α-MSH. However, systemic but not intracisternal α-MSH slightly reduced the CNS leukocyte accumulation, indicating that leukocyte extravasation is inhibited by α-MSH from the blood side. Our results show that α-MSH reduces the CNS leukocyte accumulation by its systemic action, but does not attenuate meningitis-associated intracranial complications.