Immunoglobulin A and interleukin 6 form a positive secretory feedback loop: a study of normal subjects and alcoholic cirrhotics.

Abstract

Patients with alcoholic liver cirrhosis (ALC) have high serum levels and spontaneous in vitro production of immunoglobulin (Ig) A. Deposits of IgA are also found in liver sinusoids. Increased interleukin 6 (IL-6) production is another feature of this disease. This study shows a linear correlation between increased lipopolysaccharide (LPS)-induced IL-6 production and increased spontaneous IgA and IgG secretion by peripheral blood mononuclear cells (PBMCs). PBMCs and purified monocytes isolated from healthy control subjects and patients with ALC contain elevated IL-6 messenger RNA levels and produce IL-6 in response to stimulation with soluble polymeric IgA (p-IgA) or attached monomeric IgA (m-IgA) but not with soluble m-IgA. The addition of monospecific antibody to human IL-6 inhibits spontaneous IgA production by PBMC. This inhibition is more pronounced in patients with ALC. These data provide evidence that IgA, possibly by attachment to cells possessing Fc alpha receptors and secreting IL-6, is involved in the production of this major mediator and the amplification of Ig secretion. Circulating IgA and IgA deposits could therefore initiate a process of autoamplification implicated in the development of hypergammaglobulinemia in ALC.