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

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.

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.

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-alpha1-antitrypsin complexes increased after IFN-gamma administration (P < 0.05), IFN-gamma increased the percentage of high-affinity Fcgamma-receptor (FcgammaRI) -positive neutrophils (P < 0.05), but did not affect the mean fluorescence intensity of FcgammaRI 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).

We conclude that IFN-gamma selectively affects host inflammatory mediators in humans.