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

Alpha-melanocyte-stimulating hormone (alpha -MSH) is an endogenous neuroimm unomodulatory peptide that can inhibit a broad range of inflammatory mediat ors known to be involved in the pathophysiology of bacterial meningitis. We evaluated the effect of (alpha -MSH in a rat model of pneumococcal meningi tis. 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 i ntracranial pressure, brain cytokine concentrations (IL-1 beta, IL-6, TNF-a lpha, MIP-2, and IL-10), CSF bacterial titers, and clinical parameters of d isease severity (weight loss, body temperature, and blood pressure), althou gh the treatment strongly increased the CNS concentrations of alpha -MSH. H owever, systemic but not intracisternal alpha -MSH slightly reduced the CNS leukocyte accumulation, indicating that leukocyte extravasation is inhibit ed by alpha -MSH from the blood side. Our results show that alpha -MSH redu ces the CNS leukocyte accumulation by its systemic action, but does not att enuate meningitis-associated intracranial complications. (C) 2001 Elsevier Science B.V. All rights reserved.