HUMAN alpha-1-acid glycoprotein inhibits TNF production in the CNS of rabbits with meningitis: A report of preliminary observations

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.