On interleukins 4, 6 and 10 and their interrelationship with immunoglobulins G and M in common variable immunodeficiency.

Abstract

Following culture of human peripheral blood mononuclear cells (PBMNC) from 25 normal donors and 15 patients with common variable immunodeficiency (CVID), we were unable to identify any IL10-defective patients. Clear-cut effects of IL4 could be demonstrated in controls, while in CVID all effects are less pronounced. While in both controls and CVID baseline levels of IL6, IgG and IgM were found to be correlated, this was altered by the addition of either IL4 or Poke Weed Mitogen (PWM). We therefore conclude that the inability of PBMNC to produce IL10 is not the cause of CVID in our patients. In CVID, the regulating circuitry triggered by IL4 remains principally intact, however, some subgroups of CVID behave significantly differently.

Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency

“…Recent evidence confirms that IL-4 and IL-10 production and the frequencies of polymorphisms in these genes are comparable with healthy controls, suggesting a minor, if any, role in the pathogenesis of these diseases. 30,[44][45][46][47] Furthermore, CD40 ligand (CD40L/CD154), acting as an important component of the mechanism of Ig production, is normally expressed on stimulated T lymphocytes in a predominant proportion of CVID patients. 45,46,48 Taken together, it appears that the present abnormalities of B-cell differentiation and failure to produce normal amounts of switched immunoglobulin in CVID and IgAD are not due to defect signaling through IL-4, IL-10, or IL-21 and CD40.…”

Common variable immune deficiency: Dissection of the variable

“…These observations led to early clinical trials with this cytokine, which demonstrated some clinical and immunologic benefits. [91][92][93][94] Other cytokine defects or alterations include increased IL-6 95,96 reduced interferon (IFN)γ, increased TNFα, with low or increased IL-4 [96][97][98] In contrast, IL-7, which has a role in the expansion of autoreactive T cell clones, was elevated in a subgroup of CVID patients. 99 Although increased IL-7 levels were not associated with T cell lymphopenia, they were correlated with a more frequent incidence of autoimmunity.…”

Pathogenesis of autoimmunity in common variable immunodeficiency

“…The regular feedback mechanism of IL-7 regulation seemed to fail in the small group of AI-CVID patients examined. The production of several other cytokines including IL-2, interferon (IFN)-γ, IL-4, and TNFα is altered in some CVID patients, but none of the reported alterations have been examined for their role in eliciting autoimmunity (Fischer et al, 1994; Fritsch et al, 1994; Mullighan et al, 1997). Testing the role of specific cytokines in this setting will be of great interest as it is likely to reveal potential therapeutic targets.…”