Reversible impairment in monocyte major histocompatibility complex class II expression in malnourished surgical patients.
BACKGROUND
Upregulation of major histocompatibility complex (MHC) class II antigen in response to the T-cell lymphokine interferon-gamma (IFN-gamma) is central to T cell-macrophage cooperation and immune homeostasis. We evaluated this property in malnourished surgical patients and assessed the impact of nutrition repletion with total parenteral nutrition (TPN).


METHODS
Sixty-two patients were studied: 37 malnourished and 25 controls. Whole blood was cultured with or without IFN-gamma (100 U mL-1), dual-labeled with anti-CD14 (monocyte) and anti-human leukocyte antigen-DR antibodies and analyzed by flow cytometry. Phagocytosis was measured by flow cytometry. In a second study, 10 severely malnourished patients received 5 days of TPN and MHC class II expression was measured at the end of this period.


RESULTS
The magnitude of the increase in monocyte MHC class II expression in response to IFN-gamma was significantly increased in the control group compared with the malnourished group (107% vs 53%; p < .05). This impairment directly correlated with severity of malnutrition, but did not correlate with age or disease type. The number of bacteria phagocytozed per cell was significantly decreased (p < .05) in the malnourished group. In study 2, there was a significant increase in MHC class II induction with IFN-gamma after short-term TPN (58% before vs 173% after, p < .001).


CONCLUSIONS
MHC class II induction in response to IFN-gamma is significantly impaired in malnourished patients, correlating with the severity of malnutrition. This defect is reversed by short-term TPN. These data identify the reversible loss of a key mechanism, fundamental to host defense, that may enhance the risk of infection in malnourished patients.
Welsh
F K
FK
Academic Surgical Unit, St Jame's University Hospital, Leeds, England.
Farmery
S M
SM
Ramsden
C
C
Guillou
P J
PJ
Reynolds
J V
JV
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D005802:Genes, MHC Class II / Q000187:drug effects / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016014:Linear Models; D008285:Major Histocompatibility Complex / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009748:Nutrition Disorders / Q000276:immunology*; D010289:Parenteral Nutrition, Total; D010587:Phagocytosis
D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma