Df. Moore et al., HUMAN alpha-1-acid glycoprotein inhibits TNF production in the CNS of rabbits with meningitis: A report of preliminary observations, INFLAMMATIO, 24(3), 2000, pp. 265-275
Bacterial meningitis is accompanied by an acute inflammatory response which
may be exacerbated by antibiotic treatment and subsequent killing of bacte
ria. Bacterial cell products induce the release of cytokines including TNF
alpha, which contribute to the inflammatory process. Alpha-1-acid glycoprot
ein (AAG), an acute phase reactant, is elevated during inflammation. To tes
t whether AAG has anti-inflammatory activity we examined its effect on lipo
polysaccharide-stimulated human peripheral blood mononuclear cells. Treatme
nt of the cells with AAG in vitro resulted in reduced TNF alpha production.
To test the effects of the molecule in vivo, AAG was administered intrathe
cally to rabbits with Haemophilus influenzae B lysate induced meningitis. H
uman AAG reduced TNF alpha production and leukocytosis in the cerebrospinal
fluid. Histopathology of the leptomeninges showed markedly attenuated infl
ammation. These results indicate that AAG can reduce inflammation in rabbit
s with experimental meningitis and that the effect may be directly on TNF a
lpha production by stimulated mononuclear leukocytes.