Interferon-gamma 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.


METHODS
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-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).


CONCLUSIONS
We conclude that IFN-gamma selectively affects host inflammatory mediators in humans.
de Metz
J
J
Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Hack
C E
CE
Romijn
J A
JA
Levi
M
M
Out
T A
TA
ten Berge
I J
IJ
Sauerwein
H P
HP
D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D005342:Fibrinolysis / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism
D000209:Acute-Phase Proteins; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D007371:Interferon-gamma