The effects of retinoic acid on immunoglobulin synthesis: Role of interleukin 6

Abstract

Retinoic acid (RA) and its parent compound, retinol (ROH, vitamin A), have been recognized as important immunopotentiating agents. Previous studies from our laboratory have demonstrated that RA can augment formalin-treated Staphylococcus aureus (SAC)-stimulated immunoglobulin (Ig) synthesis of cord blood mononuclear cells (CBMC). To determine the mechanism(s) by which RA modulates Ig synthesis, we studied the effects of RA on B cells and cytokine production. The addition of RA (10(-5) to 10(-10) M) to Epstein-Barr virus (EBV)-transformed B-cell clones derived from either adult or cord blood B cells augmented Ig secretion twofold. In contrast, cell proliferation was inhibited as measured by 3H-thymidine incorporation. We evaluated two cytokines known to be constitutively produced by EBV cell lines, IL-1 and IL-6. While RA had no effect on IL-1 production, IL-6 synthesis was greatly enhanced (20- to 45-fold), which was also reflected by an increase in steady-state mRNA levels for IL-6 but not TNF-alpha or TGF-beta on Northern blot analysis. Polyclonal rabbit anti-IL-6 antibodies were used to block the augmenting effects of RA on Ig synthesis of adenoidal B cells. RA-induced augmentation in IgG and IgA synthesis was blocked 58 and 29%, respectively, by anti-IL-6 antibodies. These studies suggest that the enhancing effects of RA on Ig synthesis are mediated, at least in part, by the autocrine or paracrine effects of IL-6 on B-cell differentiation.

Retinoic Acid-Induced Modulation of IL-2 mRNA Production and IL-2 Receptor Expression on T Cells

“…Purified Tcells (>95% ) were obtained from adenoidal tissues from young children (ages 2-5) as previously described [5,8], RA at optimal concentrations (10 7M) was added to T cells (1x10'' cclls/ml) in culture plates. Controls included cultures to which the DMSO solvent/media was added at the same concentration as used to dissolve the RA.…”

“…These properties range from the pro motion ofT lymphocyte proliferation to augmenting immu noglobulin (Ig) synthesis [1][2][3][4]. Our laboratory has been in terested in the effects of all-/ra«.v-retinoic acid (RA) in aug menting formalin-treated staphylococcus-stimulated B cell Ig production, and the mechanism by which this augmenta tion in Ig synthesis occurs [1,5,6], Both IL-2 and IL-6 are important cytokines for B cell differentiation and Ig secre tion [7], Recent studies in our laboratory suggest that the Ig-augmenting effects of RA is mediated, at least in part, by IL-6 through autocrine or paracrine pathways [8] This article is also accessible online at: http://www.karger.ch http://BioMedNct.com/karger direct effect of RA on T cells [1], We propose that RA can modulate other cytokines, c.g. IL-2, and that this effect may be mediated through specific RA nuclear receptors.…”

Retinoids and Opioids: Factors in the Development of HIV-Related Neurological Disease

“…For example, vitamin A deficient children were found to have lower naive and higher memory T cell percentages in blood, and these numbers were reversed by treatment with vitamin A [35] . In other human studies, vitamin A deficiency resulted in decreased cellmediated immune function [36,37] and antibody responses [36] and in lower numbers of CD4+ lymphocytes, all which also normalized following vitamin A administration [30,35,38].…”

“…In animals, retinoids have been generally shown to suppress proinflammatory responses in activated immune cells [24,25,26,27,28,29,30] . In contrast, vitamin A deficiency in experimental animals is characteristically associated with enhanced proinflammatory immune responses, effects that can be reversed by vitamin A supplementation [31,32,33,29,34] .…”

Retinoic acid enhances leukemia inhibitory factor expression in OLN-93 oligodendrocytes

“…Retinoic acid-dependent gene expression of cytokines has been described. For instance, RA induces the transcription of inflammatory cytokines including IL-6 in HL-60 granulocytes and B-cells (Grande et al 1995;Ballow et al 1996). In contrast, IL-6 production in medulloblastoma cells (Liu et al 2000) and LIF expression in human osteoblasts have been reported to be suppressed by RA (Ahmed et al 2000).…”