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

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 1 beta, interleukin 6 and tumour necrosis factor alpha (IL-1 beta, IL-6 and TNF-alpha, 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-1 beta production changed little from control, whilst IL-6 production increased markedly in CSL-serum only. TNF-alpha 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-1 beta and IL-6 production increased, whilst TNF-alpha production decreased. This only occurred 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-alpha response it otherwise stimulates. In addition, when LPS is presented in the form of IgG immune complexes, dissociation of IL-1 beta and IL-6 production from TNF-alpha production is seen but only in the presence of complement activation.(ABSTRACT TRUNCATED AT 250 WORDS)