Pooled human immunoglobulin inhibits IL-4 but not IFN-gamma or TNF-alpha secretion following in vitro stimulation of mononuclear cells with Staphylococcal superantigen.

Intravenous immunoglobulin preparations have been successfully used in many disorders, where immunomodulation rather than immunoglobulin replacement has been the goal of therapy. The exact mechanisms by which immunoglobulin exerts its immunomodulatory effects are unclear. Proposed mechanisms include modification of T cell activation and alteration to cytokine production. As intravenous immunoglobulin therapy has been used in a number of disorders where superantigens are proposed to play a role in the disease pathogenesis, we have examined the effect of in vitro human pooled immunoglobulin on cytokine production from peripheral blood mononuclear cells in response to activation with the Staphylococcal superantigen Staphylococcal enterotoxin B. The authors found inhibition of secretion of interleukin 4 (IL-4) (P<0.001) but not interferon gamma (IFN-gamma) (P=0.13) or tumour necrosis factor alpha (TNF-alpha) (P=0.66) by pooled immunoglobulin at concentrations (6 g/l) which approximate the rise in serum immunoglobulin following in vivo IVIG therapy. Mononuclear cell proliferation was also inhibited by addition of pooled immunoglobulin to superantigen stimulated cultures. These effects do not relate to specific anti-staphylococcal enterotoxin B antibodies in the immunoglobulin preparation. The authors show that pooled human immunoglobulin can differentially modulate the secretion of IL-4 and IFN-gamma in response to superantigen stimulation.