Interleukin-4-Induced IgG Subclass and IgE Secretion by Mononuclear Cells from Atopic Donors

Abstract

To investigate the effect of interleukin-4 (IL-4) on the secretion of IgG subclasses and IgE in atopic individuals, peripheral blood mononuclear cells from 10 atopic and 10 normal donors were incubated with IL-4, and the production of IgE, IgG1, IgG2, IgG3, and IgG4 was determined after a 14-day culture period. Like normal peripheral blood mononuclear cells, atopic mononuclear cells were stimulated by IL-4 to secrete IgE and IgG4, but not the other IgG subclasses. This response was in the same quantitative ranges in both donor groups. Addition of interferon gamma to IL-4-containing cultures efficiently antagonized the IL-4-induced IgE and IgG4 secretion. These results do not support the hypothesis that an atopic condition is due to a discordant effect of IL-4 on IgE compared to IgG4 production or to an altered response to the potent antagonist interferon gamma.

In vitro and in vivo effect of glucocorticoids on IgE and IgG subclass secretion

“…However, the addition of IL-4 led to enormous increases in IgE and IgG4 secretion, to a lesser extent of IgGl and even to a suppression of IgG2 production. Therefore, the co-regulation of IgG4 and IgE by IL-4 reported earlier [24][25][26] is also maintained in the presence of corticosteroids. It further suggest that, in contrary to the other subclasses, the potentiating effect of steroids on the synthesis of TgG4 and IgE is strictly dependent on the help of IL-4 producing TH-2-type cells.…”

“…cortisone enhances IgE and IgG4 only in such individuals were a sufficient amount of endogenous IL-4 is available. This has been suggested for atopic individuals [25,33] and may be the case during parasitic infection [31,33,34]. An initial increase of serum IgE in allergic patients under glucocorticoid treatment has been reported in two older studies [18,19].…”

Effects of lnterferon-Alpha-2b on the Clinical Course, Inflammatory Skin Infiltrates and Peripheral Blood Lymphocytes in Patients with Severe Atopic Eczema

“…Many immunological abnormalities, including diminished interferon (IFN) production by mononuclear cells, probably involved in pathogenetic events of AE, have been elucidated [4][5][6][7], Although the serum IgE levels and severity of disease do not correlate, a possible role of IgE/allcrgen complexes bound on Fee receptors on intraepidermal Langerhans cells (LC) is being discussed [2,[8][9][10][11][12]. Soluble CD23 was shown to be increased in the serum of patients with atopic conditions [13], In healthy individuals and patients with AE the IgE production of B cells as well as CD23 (low af finity Fc receptor for IgE) expression on immunocompe tent cells is markedly influenced by T-cell-derived cyto kines like IL-4 and IFNs [14][15][16][17]. Additionally, previous studies demonstrated that IL-4 induces IgE synthesis [18], CD23 expression [19] as well as the expression of cellular adhesion molecules like LFA-1 and LFA-3 [20], Peripheral blood lymphocytes (PBL) of patients with AE responded to IL-4 by an increased proliferation in comparison to healthy individuals [21], Immune IFN, prostaglandin E2 (PGE2) as well as a-IFN were shown to suppress IL-4-depcndent enhance ment of IgE synthesis [19,[22][23][24][25].…”

Reduced IL-4 associated antibody responses to vaccine in early pre-diabetes

“…In the current study, antigen-specific antibody subclasses were used to measure the magnitude and quality of responses to these antigens. The subclass response is an indirect measure of T-cell phenotype in the mouse [11,12], while in humans IgG4 or IgE antibody production or both are promoted by the T helper (Th) 2 cytokines IL-4 and IL-13 [13,14,15,16]. Our finding of a marked impairment in the IL-4 associated IgG4 response to tetanus toxoid (TT) in children with early established pre-diabetes supports the concept of a generalized immune deviation in the presence of beta-cell autoimmunity.…”