Regulation by IFN-beta of inducible nitric oxide synthase and interleukin-12/p40 in murine macrophages cultured in the presence of Chlamydia pneumoniae antigens

Chlamydia pneumoniae has been demonstrated in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), Interferon-beta (IFN-beta) has f avorable effects on the clinical course of MS. We investigated whether the beneficial effects of IFN-beta in MS may involve its role in regulating nit ric oxide (NO) and interleukin-12 (IL-12) in macrophages, as these immune m odulators form part of the innate immune response to intracellular pathogen s, such as C, pneumoniae, Murine macrophages in cultures exposed to element ary body antigens or recombinant major outer membrane protein (rMOMP) of C, pneumoniae demonstrate a significant increase in NO as well as production of IL-12/p40 in culture supernatants compared with basal levels, Addition o f murine IFN-beta increased NO activity in murine macrophages cultured with chlamydial antigens, Addition of neutralizing anti-IFN-beta antibody preve nted the NO increase. In contrast to its effect on inducible NO synthase (i NOS), IFN-beta reduced induction of IL-12/p40 following culture with either elementary body antigens or rMOMP, Inhibition was reversed with anti-IFN-b eta antibody. If C, pneumoniae infection is responsible for the inflammator y response in the pathogenesis of MS, the beneficial effects of IFN-beta in MS may be due to its enhancing intracellular NO activity while inhibiting secretion of the proinflammatory cytokine, IL-12.