Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency.

BACKGROUND: Transient hypogammaglobulinemia of infancy and isolated IgA deficiency are characterized by normal numbers of circulating B lymphocytes. It is likely that no single abnormality, but rather different factors, may be relevant for the delayed onset of IgG synthesis in transient hypogammaglobulinemia or for the differentiation defect of B cells in IgA deficiency. These factors may include defective production of cytokines or an abnormal response of B cells to various mediators. Alternatively, some cytokines may act as inhibitory factors of B-cell function.

METHODS: The ability of peripheral blood mononuclear cells from children with proved or probable transient hypogammaglobulinemia (30 patients) and IgA deficiency (15 patients) to secrete several cytokines on stimulation with phytohemagglutinin in vitro was analyzed.

RESULTS: An enhanced production of tumor necrosis factor (TNF)-alpha, TNF-beta, and IL-10 was observed in transient hypogammaglobulinemia; whereas secretion of IL-1, IL-4, and IL-6 was essentially similar in the control and patient groups. Increased frequency of mononuclear cells secreting TNF-alpha was seen in the patient groups. Apart from elevated production of TNF-alpha, no other abnormalities in cytokine synthesis in selective IgA deficiency were observed. In vitro observations showed that exogenously added TNF-alpha and TNF-beta inhibited IgG and IgA secretion by pokeweed mitogen-stimulated mononuclear cells. During follow-up of 10 children, normalization of serum IgG level was associated with a decrease in previously elevated TNF-alpha and TNF-beta production, but IL-10 production remained unchanged.

CONCLUSION: These results suggest that TNF may be involved in the regulation of IgG and IgA production and can be associated with an arrest of IgG and IgA switch of B cells in hypogammaglobulinemia. The balance between TNF and IL-10 may be important for the normal development of IgG-secreting B cells.