To investigate the effect of immunoglobulins on survival, activation, reactive oxygen species (ROS) and cytokine production of microglia exposed to ketone bodies.

Hippocampal gliosis and activated microglia have been reported in   diabetic ketoacidosis (DKA) and have been associated to cognitive impairment observed in DKA patients. immunoglobulins, a well-established therapy of several autoimmune diseases, inhibited antibody mediated demyelination and microglia activation in organotypic cerebellar slice cultures.

Human microglia CHME5 cell line was treated with immunoglobulin after exposure to acetoacetate (AcAc). The change in their viability, ROS production, apoptosis and cytokine profiles was investigated.

Immunoglobulin did not prevent increased microglial apoptosis observed 3 days after AcAc exposure.  However it did attenuate ROS that started 1 hour after AcAc exposure.   Increased  cytokines expression occurred 1 hour after AcAc treatment, however, only IL-13, IL-1β, and IL-6 increased more than 2-folds.   The elevation of cytokine expression induced by AcAc was suppressed 1 hour after treatment with immunoglobulins. However, as time extended, immunoglobulins promoted the expression of most cytokines including pro- and anti- inflammatory cytokines, especially TNF-α, IL-10, and IL-13.The anti-inflammatory cytokines IL-4, IL-10 and IL-13 expression  profiles were similar in the IG treated microglia:   after an initial drop within 1h after IG treatment,  their expressions increased within 24 h and was superior to untreated microglia. Their expressions continued increase 72h after immunoglobulin treatment and was more than 2 folds superior to untreated microglia. These findings suggest that there is a tendency to more robust increase of anti-inflammatory cytokines over time compared to pro-inflammatory cytokines in immunoglobulin treated microglia after AcAc exposure.

Immunoglobulin  suppressed microglia activation induced by ketone bodies, attenuated oxidative stress and transiently inhibited cytokines expression without affecting apoptosis.

These results warrant further experimental work on the role of microglia and potential benefit of immunoglobulin in brain structural changes induced by DKA.