The role of interleukin 6 in interferon-gamma production in thermally injured mice

Following traumatic injury, patients suffer from compromised immunity incre asing their susceptibility to infection. Previous studies from this laborat ory demonstrated that female BALB/c mice subjected to a 15% total body surf ace area (TBSA) scald injury exhibit a decrease in cell-mediated immunity 1 0 days post-burn. Studies described herein revealed that concanavalin A (Co n A; 2 mug/ml)-stimulated splenocytes from sham treated animals produced 35 57 +/- 853 pg/ml of IFN-gamma while splenocytes from burn injured animals r eleased two-fold more cytokine (P<0.05), To determine whether leukocyte pro duction of IFN-<gamma> was under the influence of macrophages, splenic macr ophage supernatants generated from burned animals were incubated with splen ic lymphocytes from sham and burn animals. The amount of IFN-gamma released by lymphocytes from sham animals increased when cultured with macrophages from burned mice (P<0.05). This suggests that the increase in IFN-<gamma> p roduction by unfractionated splenocytes in burned mice relative to sham tre ated animals is macrophage-dependent. Macrophage supernatants from burned m ice released twice as much IL-6 as supernatants from sham animals (P<0.05), and when IL-6 was blocked in vivo, the amount of IFN-<gamma> production in burned mice decreased to sham levels (P<0.05), Thus, IL-6 mediates IFN-<ga mma> production following burn. (C) 2000 Academic Press.