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

Background It is suggested that interferon-gamma (IFN-gamma), 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-gamma in human host inflammatory responses, however, has not been studied. Design In a placebo-controlled trial we studied the acute effects of IFN-gamma 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-gamma increased plasma levels of interleukin-6 (IL-6), IL-8 and IFN-gamma -inducible protein-10 (IP-10) (P < 0.05), but did not affect plasma levels of other cytokines (IL-4, IL-10, tumour necrosis factor-<alpha>, 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-<alpha>1-antitrypsin complexes increased after IFN-gamma administration (P < 0.05, IFN-<gamma> increased the percentage of high-affinity Fc gamma -receptor (Fc gamma RI) -positive neutrophils (P < 0.05), but did not affect the mean fluorescence intensity of Fc<gamma>RI on neutrophils. Procoagulant and profibrinolytic effects of IFN-gamma were evidenced by increased plasma levels of prothrombin fragment F1+F2, tissue-plasminogen activator and plasmin-alpha2-antiplasmin complexes (P < 0.05). Conclusion We conclude that IFN-<gamma> selectively affects host inflammatory mediators in humans.