Diminished Response to Interleukin-10 and Reduced Antibody-Dependent Cellular Cytotoxicity of Cord Blood Monocyte-Derived Macrophages

Abstract

Monocyte-derived macrophage (M⌽) subsets are generated by antagonistic induction pathways. A helper M⌽-type (Mh-M⌽) is induced by interferon gamma (IFN-␥), whereas a cytotoxic M⌽-type (Mc-M⌽), induced by interleukin-10 (IL-10), is a potent mediator of antibody-dependent cellular cytotoxicity (ADCC). Compared with M⌽ from healthy adults [peripheral blood monocyte-derived macrophages (PBM⌽)], cord blood M⌽ (CBM⌽) were found less capable of generating Mh-M⌽. Here we tested the hypothesis that their generation of Mc-M⌽ via IL-10 is also impaired. M⌽ surface markers were phenotyped. IL-10 protein and mRNA production were detected after stimulation [␣CD3 monoclonal antibody (mAb)]. CBM⌽ or PBM⌽ were co-cultured with M⌽-depleted mononuclear cells of adults and CD4-targeting antibodies as models for ADCC were added. In cord blood, we found diminished ␣CD3-induced IL-10 protein and mRNA production (p Ͻ 0.05 versus adults). Basal CD16 and HLA-DR expressions on CBM⌽ of preterm and full-term neonates were lower (p Ͻ 0.05 versus PBM⌽). IL-10 had reduced effects on CD16 up-and HLA-DR down-modulation on CBM⌽ (p Ͻ 0.05 versus PBM⌽). CD4-directed receptor modulation and deletion were reduced in the presence of CBM⌽ (p Ͻ 0.05 versus PBM⌽). IL-10 failed to enhance their ADCC capacity, which was in contrast to PBM⌽ (p Ͻ 0.05). These data suggest that CBM⌽ have an impaired cytotoxic capacity via lower sensitivity toward IL-10. (Pediatr Res 60: 152-157, 2006)

Immunomodulatory effects of a 3.2kDa polypeptide from velvet antler of Cervus nippon Temminck

“…Th1-type cells secrete IL-2, IFN-γ, IL-12 and TNF-α while Th2-type cells secrete IL-4 and IL-10. The communication network between Th1 and Th2 cytokines may be synergistic or antagonistic toward lymphocyte proliferation and differentiation [19]. In this study, cytokine-detection ELISA results showed that nVAP32 significantly stimulated the release of Th1 cytokines (IL-2, IL-12, IFN-γ and TNF-α) while decreased the release of Th2 cytokines (IL-4, IL-10), and thus the Th1/Th2 arms of the immune system were modulated.…”

Antenatal inflammation and lung injury: prenatal origin of neonatal disease

“…54,70 Many factors affect the modulation of the inflammatory response, such as antenatal steroid therapy, resuscitation, surfactant therapy, mechanical ventilation, oxygen toxicity and pulmonary and/or systemic infection. 7 Along with the immaturity of the preterm immune system, 71 antenatal and postnatal factors may also condition and modulate the pulmonary inflammation. 7 Future research must aim at dissecting the involved pathways to better discern beneficial effects, such as lung maturation, from adverse effects, such as delay in lung development.…”

Diminished Phagocytosis-Induced Cell Death (PICD) in Neonatal Monocytes upon Infection with Escherichia coli

“…Modifying monocyte apoptosis may be a target for future interventions in sepsis. (Pediatr Res 63: [33][34][35][36][37][38] 2008) …”