Modulation of lymphocyte and monocyte activity after intravenous immunoglobulin administration in vivo

Abstract

SUMMARYIn 12 patients with primary hypogammaglobulinaemia we investigated the in vivo effect of one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) on lymphocyte subsets and monocytes in peripheral blood, on plasma levels of soluble factors reflecting monocyte and lymphocyte activity and on lymphocyte proliferation and generation of reactive oxygen species (ROS) from monocytes analysed in vitro. Several immunological changes were induced by IVIG infusion. First, there was a significant decrease in CD4 þ /CD8 þ lymphocyte ratio in peripheral blood, reflecting a significant increase in circulating numbers of CD8 þ lymphocytes. Second, although there was no significant change in plasma levels of soluble CD8 antigen, there was a significant decrease in soluble CD8 antigen/CD8 þ lymphocyte ratio, suggesting a down-regulation of CD8 þ lymphocyte activity. Third, there was a significant increase in plasma levels of neopterin, suggesting in vivo activation of monocytes/ macrophages. Fourth, the was a down-modulation of mitogen-stimulated lymphocyte proliferation in vitro, and this down-regulation was significantly correlated with the increase in plasma neopterin levels. Finally, there was a significant decrease in zymosan-stimulated, but not in phorbol myristate acetatestimulated, ROS generation from monocytes as evaluated by nitroblue tetrazolium reduction. The ability of IVIG administration in vivo to down-modulate lymphocyte proliferation and ROS generation from monocytes in patients with persistent immune activation may be relevant for the clinical effects of IVIG in a variety of immune-mediated disorders.

Anti-D initially stimulates an Fc-dependent leukocyte oxidative burst and subsequently suppresses erythrophagocytosis via interleukin-1 receptor antagonist

“…Few reports have studied the effects of intravenous immunoglobulin or anti-D on the generation of ROS. With respect to intravenous immunoglobulin, Aukrust et al 14 demonstrated that intravenous immunoglobulin decreased monocyte ROS production, whereas Nakatani et al 15 showed that intravenous immunoglobulin could significantly enhance ROS in endothelial cells. The reasons for these discrepancies are unknown but may reflect the ability of intravenous immunoglobulins to cause different effects, depending on the cells studied.…”

Skin Score Decrease in Systemic Sclerosis Patients Treated with Intravenous Immunoglobulin - A Preliminary Report

“…Possible mechanisms for the efficacy of IVIg in autoimmune diseases include the blockade of phagocytic cell Fc receptors; immunomodulation of lymphocyte differentiation and effector functions, including B-cell immunoglobulin production and T-cell suppressor activity; perturbation of inflammatory mediator or immunomodulator levels, including cytokines, chemokines, complement pathways, eicosanoids, steroids and neuropeptides; the solubilization of immune complexes; and anti-idiotypic manipulation of autoantibodies [27][28][29][30][31][32][33][34][35]. IVIg can also induce the production of interleukin-1 receptor antagonist and suppress the production of tumour necrosis factor-a and interleukins-1 and -6, thus providing a possible explanation for its beneficial effect in the treatment of conditions associated with fibrosis [36,37].…”

Neopterin: a review

“…Therefore, neopterin estimations may under these circumstances be more useful than erythrocyte sedimentation rate (ESR) estimations, which has a long latency period (95).…”

“…Increased neopterin levels also followed withdrawal of cyclosporine A, since this drug inhibits secretion of interferon-g by T cells (27). A significant increase in plasma levels of neopterin was seen in patients with primary hypogammaglobulinaemia after one bolus injection (400 mg/kg) of intravenous immunoglobulin (IVIG) (95). A fast increase of neopterin values in sera of advanced cancer patients was seen during subcutaneous treatment with recombinant interleukin-2 (96).…”