In vivo modulation of cytokine synthesis by intravenous immunoglobulin

We examined the effects of intravenous immunoglobulin (IVIG) on cytokine regulation in vivo using samples taken before and after replacement-dose (200–400 mg/kg) IVIG in a group of patients with common variable immunodeficiency (CVID) and X-linked agammaglobulinaemia (XLA). The intracellular cytokine content of CD4+ and CD8+ lymphocytes, and their CD28+/− subsets, were measured following in vitro activation with phorbol myristate acetate (PMA) and ionomycin. The cytokines IL-2, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), 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 expression in CD4+ (and CD4+28−) cells and an increase in TNF-α expression in CD8+28− cells following IVIG in CVID, but not in XLA patients. IFN-γ and CD69 expression were not affected by IVIG infusion. This increase in TNF-α and IL-2, combined with unchanged IFN-γ expression, is evidence against the putative ‘anti-inflammatory’ role of IVIG, and may explain the failure of resolution of granulomata in CVID patients treated with IVIG alone

No effect of intravenous immunoglobulins on cytokine-producing lymphocytes in secondary progressive multiple sclerosis.

Contains fulltext : 49591.pdf (publisher's version ) (Closed access)Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) disease activity and improving disability scores. However, the mechanism by which this beneficial effect is achieved remains unclear. An effect of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role in the disease process - has been postulated in a number of animal and ex vivo studies. Hence, we performed a study on 34 patients with secondary progressive (SP) MS being treated with monthly IVIG or placebo for two years according to the protocol of the ESIMS study. Clinical outcome measures and cytokine production (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were recorded in all patients and compared with respect to the treatment group. Against our expectations, IVIG did not reduce the relapse rate or the progression of disability or cytokine production. Our data argue against an enduring immunomodulating effect of IVIG, at least in SPMS