Inhibition of microglia multinucleated giant cell formation and induction of differentiation by GM-CSF using a porcine in vitro model

Multinucleated giant cell (MNGC) formation is an important histopathologic feature of AIDS dementia complex and tuberculous meningitis. We investigated the effect of several cytokines (GM-CSF, IFN-γ, TNF-α, IL-3) and other stimuli (vaso-I, LPS, PMA) on MNGC formation in vitro by microglia from porcine neonatal brain. GM-CSF dose-dependently inhibited giant cell formation at physiological conditions (10 ng/ml) up till 4 days in culture. When confronted with a high concentration (1 μg/ml) they were 5.5 times less likely to form MNGC and 3.3 times more likely to develop a ramified morphology. In contrast, interferon-γ (6 ng/ml) doubled the formation of MNGC. GM-CSF primed (4 days) microglia also produced significantly higher amounts of superoxide after PMA-stimulation. We conclude that GM-CSF leads microglia to a specific activation other than MNGC formation. Comparison of the present results with earlier reports on rodents reveals important inter-species differences.