Dialyzable Leukocyte Extract Stimulates cAMP in Tγ Lymphocytes

Abstract

Dialyzable leukocyte extract (DLE) from human blood leukocytes gave a 3- to 8-fold increase in the cAMP concentration after addition to purified lymphocytes. No significant change in cGMP was observed. When purified lymphocytes were separated into T cells and non-T cells by an E-AET rosette technique the cAMP response was most pronounced in T cells. When further separating T lymphocytes into T cells with Fc receptors for IgG and T cells with Fc receptors for IgM (T gamma and T mu lymphocytes), the increase in cAMP following stimulation was specifically conferred to T gamma lymphocytes. Our findings may support the concept that DLE activates T gamma lymphocytes, leading to an increase in suppressor cell function.

Dialyzable Leukocyte Extract differentially regulates the production of TNF?, IL-6, and IL-8 in bacterial component-activated leukocytes and endothelial cells

“…We also observe a similar effect in LPS-stimulated monocytes. In earlier studies with DLE, other groups reported accumulation of cyclic nucleotides by DLE in lymphocytes and monocytes [13,30]. Our findings support the notion that the increase of cAMP induced by DLE could be related to the DLE effect on proinflammatory cytokine production.…”

“…Pharmacological agents that elevate intracellular cAMP levels like rolipram, a phosphodiesterase (PDE) IV inhibitor, and dibutyryl cyclic AMP, inhibit the production of TNFa in response to LPS stimulation in whole blood and monocytes [12]. In addition, Herlin et al reported that DLE from human blood leukocytes elevates cAMP levels in lymphocytes [13]. In the present study we observed that DLE differentially regulates the expression of proinflammatory mediators TNFa, IL-6, and IL-8, upon binding of Gram-negative and Gram-positive cell wall components to TLRs on leukocytes and endothelial cells.…”

Transfer Factor in Atopic Dermatitis

“…We also found a reduction in the total number of T lymphocytes in blood, but this does not indicate any specific immunolog ical impairment. The slight, but sustained depression of monocyte cyto- toxicity is in accordance with our previous results showing unchanged monocyte cytotoxicity through periods of clinical exacerbation and remis sion of AD [11], We have previously shown that TF is able to induce a significant increase in cAMP in T-gamma lymphocytes [4], If the T-gamma lympho cyte population contains nonspecific suppressor cells for IgE [8], then TF may be of clinical value in AD.…”

Transferon™, a peptide mixture with immunomodulatory properties is not immunogenic when administered with various adjuvants

“…hDLE have a demonstrated value as coadjuvants in treating diseases with an inflammatory component (Pizza et al 1996;Berron-Perez et al 2007;Hernandez et al 2013), such as herpes zoster infections (Estrada-Parra et al 1998) and atopic dermatitis (Flores Sandoval et al 2005), based on their immunomodulatory properties. Though mechanisms of action of hDLE are not fully understood, they have been associated with: toll-like receptor (TLR) stimulation (Garcia-Hernandez et al 2014); induction of transcription factors and second messengers in cd T-lymphocytes (Herlin et al 1981); and, modulation of tumor necrosis factor (TNF)-a, interferon (IFN)-c, and interleukin (IL)-6 levels in human and mouse serum (Hernandez et al 2013;Salinas-Jazmin et al 2015).…”