Alpha‐globulins suppress human leukocyte tumor necrosis factor secretion

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Abstract
The secretion of tumor necrosis factor (TNF) by human peripheral blood mononuclear cells was suppressed by either whole human plasma α‐globulins or purified α1 acid‐glycoprotein, α1‐antitrypsin and α2‐macroglobulin in a concentration‐dependent manner. α1‐Antitrypsin was found to be the most suppressive of the purified proteins tested and completely blocked TNF release at concentrations above 1.25 mg/ml. Both α1‐acid glycoprotein and α1‐antitrypsin blocked TNF secretion by leukocytes which were simultaneously stimulated with either recombinant human interferon‐γ (IFN‐γ) or lipopolysaccharide (LPS). IFN‐γ and LPS‐activated cells were also susceptible to suppression mediated by these two α‐globulins and the inhibition produced by 5 mg/ml α1‐antitrypsin was greater than that caused by either 1 m̈M prostaglandin E2 or 10 ng/ml transforming growth factor‐pi. The level of TNF mRNA in TNF‐secreting and α‐globulin‐suppressed cells was examined and found to be equal in both groups. The suppressive effect of whole α‐globulins was confined to the inhibition of TNF secretion and these plasma proteins had no effect on the cytolytic activity of the recombinant cytokine as measured on murine L‐929 target cells. Thus the α‐globulins, which are a major fraction of the circulating plasma proteins, may function in TNF homeostasis by controlling TNF secretion without inhibiting the biological activity of the released cytokine.