Interferon gamma administration increases monocyte HLA-DR antigen expression but not endogenous interferon production
D. H. Livingston, P. A. Loder, S. M. Kramer, U. E. Gibson and H. C. Polk Jr
Department of Surgery, UMD-New Jersey Medical School, Newark.
OBJECTIVE: To determine the effect of the adjuvant administration of
interferon gamma on monocyte HLA-DR antigen expression and
mitogen-stimulated interferon gamma production following injury. DESIGN:
Double-blind, randomized, placebo-controlled trial. SETTING: University
Hospital, Newark, NJ, a level I trauma center. PATIENTS: Persons older than
16 years with an Injury Severity Score greater than 20 and documented
bacterial contamination at the time of injury (N = 98). INTERVENTIONS:
Recombinant human interferon gamma (n = 46; 0.1 mg subcutaneously) or
placebo (n = 52) was given for 10 days following injury. OUTCOMES:
Incidence of major infection, monocyte and lymphocyte cell surface antigen
expression, and interferon gamma production at multiple time points
following injury. RESULTS: Peripheral monocyte HLA-DR was measured as
percent of cells staining positive and as mean channel fluorescence. Both
values were significantly increased in the interferon gamma group compared
with the placebo group on days 3, 5, 8, and 11. The incidence of major
infection was unaffected by interferon gamma administration. Infection
decreased percent of HLA-DR-positive monocytes and mean channel
fluorescence as compared with noninfected patients on postinjury days 8 and
11 in the placebo group but not in the interferon gamma group. Interferon
gamma production improved from 3 +/- 3 U/mL on day 1 to 15 +/- 10 U/mL by
day 30 but was always significantly lower than normal (25 +/- 3 [mean +/-
SD] U/mL). Interferon gamma production was unaffected by either infection
or interferon gamma administration. CONCLUSIONS: Interferon gamma
administration after injury stimulated monocyte HLA-DR antigen expression
and density but failed to improve interferon gamma production, a
T-cell-mediated function. The incidence of infection was not decreased by
the administration of interferon gamma for 10 days. Improvement in monocyte
HLA-DR antigen expression did not correlate with a global restoration of
immune function, and other interventions will be necessary to decrease
infection after injury.
