The effects of IgG and immune complexes on the endotoxin-induced cytokine response

Abstract

Cytokine induction following stimulation by endotoxin (LPS) was investigated in human peripheral whole blood. Blood cells were suspended in autologous plasma diluted in basal medium (BM-plasma) or Compound Sodium Lactate Solution (CSL-plasma), or in autologous serum diluted in CSL. Induction of interleukin 1β, interleukin 6 and tumour necrosis factor α (IL-1β, IL-6 and TNF-α, respectively) was investigated following incubation of blood cells with LPS, IgG (Sandoglobulin) alone, or preformed LPS/IgG immune complexes. All three cytokines were induced by LPS alone. With 30 mg/ml Sandoglobulin alone, IL-1β production changed little from control, whilst IL-6 production increased markedly in CSL-serum only. TNF-α production increased slightly in BM-plasma and CSL-plasma, but not in CSL-serum. Lower concentrations of Sandoglobulin did not affect cytokine production. Upon stimulation with LPS/Sandoglobulin immune complexes, a trend in cytokine production was seen compared with the response to LPS alone: IL-1β and IL-6 production increased, whilst TNF-α production decreased. This only occured in CSL-plasma and CSL-serum. Complement activation was present only in CSL-plasma and CSL-serum. Thus in the presence of complement activation and/or serum, Sandoglobulin can induce IL-6 production whilst suppressing the small TNF-α response it otherwise stimulates. In addition, when LPS is presented in the form of IgG immune complexes, dissociation of IL-1β and IL-6 production from TNF-α production is seen but only in the presence of complement activation. These results suggest an important role for complement activation in the modulation of cytokine production, and support the use of whole blood preparations for investigating the response to LPS.