Lactoferrin effects on immune response in critically ill
© Current Science Ltd 1997
Published: 1 March 1997
We have studied in vitro the effect of lactoferrin on the proliferative response of peripheral blood mononuclear cells and their ability to produce IL-6 and TNF-alpha in three groups of patients - septic survivors, septic non-survivors and patients after multiple organ injury. Lactoferrin is an iron-binding glycoprotein with a wide spectrum of biological activities (Ann Rev Nutr 1995, 15:93). It may contribute to the protection against pathogens and their metabolites by enhancing phagocytosis, cell adherence, and controlling release of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha.
We investigated 53 adult patients (40 men and 13 women, aged 15-73 years) meeting the ACCP/SCCM criteria of sepsis or sepsis shock (Crit Care Med 1992, 20:864) who were treated in our intensive therapy unit for peritonitis, pancreatitis. ARDS, or major trauma. The mean APACHE II score on admission was 21.85 and 18.5 in septic and post-traumatic patients, respectively. The patients were divided into three groups: multiple trauma (T, n = 10), septic survivors (SS, n = 14), septic non-survivors (SN, n = 19). The control group consisted of 13 healthy volunteers.
The proliferative response of PBMC in vitro was tested using 3-day culture with mitogens (PHA, LPS). The cell proliferation was measured using MTT colorimetric method. The activity of TNF-alpha and IL-6 was measured with bioassary using indicator cell lines WEHI-164.13. and 7TDI. respectively.
Lactoferrin significantly inhibited PHA-induced proliferation in three groups of patients during the whole monitoring period (P < 0.05). Lactoferrin alone appeared to be a very good inducer of IL-6. The effect of lactoferrin on LPS-induced IL-6 production by leukocytes was also stimulatory. The influence of lactoferrin on IL-6 production was very significant especially in the group of septic survivor patients. Lactoferrin appeared to be a very good inducer of TNF-alpha, however, its action varied considerably among particular groups of patients. In trauma patients lactoferrin exhibited a moderate up-regulatory activity. Most significant stimulatory effects of lactoferrin were seen in septic survivor group, which resulted in a permanently high TNF-alpha production during the whole monitoring period. Quite different response pattern was observed in the group of septic non-survivor patients; their cells ability to produce TNF-alpha was low and the effect of lactoferrin was not so significant as in the survivor group.
(i) Lactoferrin seems to exert a beneficial action on the immune response. It slightly decreases the PHA-induced lymphocyte proliferation, (ii) Lactoferrin is a good inducer of IL-6 and TNF-alpha production. It cannot, however, break through lymphocyte anergy, as measured in LPS-induced cytokine secretion test.