Interferon‐γ in healthy subjects: selective modulation of inflammatory mediators

Abstract

Background It is suggested that interferon‐γ (IFN‐γ), like other cytokines, is a mediator in the host inflammatory response, which could be of importance in the pathophysiology of sepsis. The role of IFN‐γ in human host inflammatory responses, however, has not been studied. Design In a placebo‐controlled trial we studied the acute effects of IFN‐γ administration on host inflammatory mediators in healthy men: i.e. the cytokine/chemokine cascade system, acute‐phase proteins, activation markers of the innate cellular immunity and coagulation/fibrinolysis parameters. Results IFN‐γ increased plasma levels of interleukin‐6 (IL‐6), IL‐8 and IFN‐γ‐inducible protein‐10 (IP‐10) (P < 0·05), but did not affect plasma levels of other cytokines (IL‐4, IL‐10, tumour necrosis factor‐α, IL‐12p40/p70). Plasma concentrations of C‐reactive protein and secretory phospholipase A2 both increased (P < 0·05). Plasma levels of the leucocyte activation marker elastase‐α1–antitrypsin complexes increased after IFN‐γ administration (P < 0·05), IFN‐γ increased the percentage of high‐affinity Fcγ‐receptor (FcγRI) ‐positive neutrophils (P < 0·05), but did not affect the mean fluorescence intensity of FcγRI on neutrophils. Procoagulant and profibrinolytic effects of IFN‐γ were evidenced by increased plasma levels of prothrombin fragment F1 + F2, tissue‐plasminogen activator and plasmin‐α2–antiplasmin complexes (P < 0·05). Conclusion We conclude that IFN‐γ selectively affects host inflammatory mediators in humans.