Human intravenous immunoglobulin modulates monokine production in vitro

The effects of human immunoglobulin preparations for intravenous use (IVIg) on in vitro-induced monokine production were studied. Individual peripheral blood monocytes, obtained from healthy blood donors, which produced interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) after in vitro stimulation, were identified by cytokine-specific monoclonal antibodies (mAb) and indirect immunofluorescence technique. Lipopylosaccharide (LPS) or Borrelia burgdorferi spirochetes (Bb) were used to induce TNF-alpha and IL-6 production in cultures. Peak synthesis occurred 2.5 hr after initiation of the cultures in the majority of the monocytes, but not at all in lymphocytes. The monocytes were identified by two-colour staining using a monocyte-specific mAb. IL-6 was produced by 64 +/- 8% or 71 +/- 9% (means +/- SD) of the non-IVIg-exposed monocytes after LPS or Bb stimulation, respectively (n = 12). A dose-dependent and significant reduction of the number of IL-6-producing cells was noted in the IVIg-supplemented cultures (P less than 0.003). In these cultures 24 +/- 12% or 29 +/- 12% of the monocytes made IL-6 in response to LPS or Bb. Kinetic studies indicated a sustained significant inhibition of IL-6 production during 24 hr of culture (P less than 0.001). In contrast, TNF-alpha synthesis was not inhibited by IVIg. LPS or Bb stimulation resulted in 47 +/- 18% or 69 +/- 7% TNF-alpha producing cells versus 48 +/- 9% or 59 +/- 8% in IVIg-supplemented cultures. These results indicate down-regulation of IL-6, but not TNF-alpha production, by IVIg. A direct antigen neutralization is an unlikely explanation for the divergent effects observed on monokine production after IVIg addition.