Differential modulation of cord blood and peripheral blood monocytes by intravenous immunoglobulin

Immunoglobulins (IVIG) have been shown to be useful in adults suffering from sepsis. In contrast, prophylactic and curative IVIG trials failed to show beneficial effects in neonates. We tested the hypothesis that IVIG, have different effects on monocytes from cord blood (CBMO) and peripheral blood monocytes from adults (PBMO) with respect to survival, phenotype, and function.

Mononuclear cells, or purified monocytes, were cultured in 5% human serum, incubated with polyvalent IVIG (1 mg/ml), stimulated with green fluorescent protein (GFP)-labeled Escherichia coli (E. Coli-GFP), Interferon-γ (IFN-γ, 50 U/ml), or the T cell mitogen anti-CD3 monoclonal antibody, αCD3-mAb, (5 μg/ml). Phagocytosis, phenotype, T cell proliferation, and apoptosis were assessed by flow cytometry.

IVIG enhanced phagocytosis in PBMO or CBMO when infected directly after isolation, while IVIG had no effect on monocytes cultured 48 h prior to infection. In contrast to PBMO, IVIG inhibited the IFN-γ mediated up-regulation of CD80, CD86, and HLA-DR on CBMO. In the presence of IVIG, stimulation with αCD3 in cord blood enhanced deletion, inhibited blast formation and CD28 up-regulation of T cells (P < 0.05 vs. T cells from adults). IVIG induced monocyte apoptosis, associated with up-regulation of Annexin V and loss of nuclear DNA, which was more pronounced in CBMO. Although phagocytosis induced cell death (PICD) was lower in CBMO (P < 0.05 vs. PBMO), the addition of IVIG enhanced PICD levels of CBMO to the extent of PBMO.

IVIG inhibits co-stimulatory receptors and functions of CBMO and induces apoptosis. These findings may be of clinical relevance for the failure of IVIG benefit in neonatal sepsis.