In vivo modulation of cytokine synthesis by intravenous immunoglobulin

We examined the effects of intravenous immunoglobulin (IVIG) on cytokine re gulation in vivo using samples taken before and after replacement-dose (200 -400 mg/kg) IVIG in a group of patients with common variable immunodeficien cy (CVID) and X-linked agammaglobulinaemia (XLA). The intracellular cytokin e content of CD4(+) and CD8(+) lymphocytes, and their CD28(+/-) subsets, we re measured following in vitro activation with phorbol myristate acetate (P MA) and ionomycin. The cytokines IL-2, interferon-gamma (IFN-gamma) and tum our necrosis factor-alpha (TNF-alpha), and the early activation marker CD69 , were assessed by four-colour flow cytometry of whole blood cultures taken before and after IVIG infusion. There was a significant increase in IL-2 e xpression in CD4(+) (and CD4(+)28(-)) cells and an increase in TNF-alpha ex pression in CD8(+)28(-) cells following IVIG in CVID, but not in XLA patien ts. IFN-gamma and CD69 expression were not affected by IVIG infusion. This increase in TNF-alpha and IL-2, combined with unchanged IFN-gamma expressio n, is evidence against the putative 'anti-inflammatory' role of IVIG, and m ay explain the failure of resolution of granulomata in CVID patients treate d with IVIG alone.