The 1996 Moyer Award. Effects of endotoxin on the Th1/Th2 response in humans.
Monocyte/T-cell interactions play a critical role in the systemic response to infection. Distinct patterns of cytokines are produced by two different types of T-helper cells (Th). Th1 cells secrete interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), whereas Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13. In volunteers systemic endotoxin administration initiates many features of gram-negative sepsis including cytokine release, but the patterns (i.e., Th1/Th2 patterns) have not yet been studied. In this institutional review board-approved study we investigated the effect of an intravenous bolus of endotoxin from Escherichia coli (4 ng/kg body weight) on the Th1/Th2 response in four female and four male volunteers (mean age 27.1 +/- 0.8 years). Plasma cytokine levels for IL-2, IL-4, IL-10, IL-12, and IFN-gamma and heart rate, mean arterial pressure, temperature, white blood cell, and differential blood count were determined before and hourly for 5 hours after endotoxin administration. All volunteers had tachycardia, decreased mean arterial pressure, fever, and leukocytosis. IL-10 was significantly (p < 0.05) elevated (9.4 +/- 3.9 pg/ml vs 60.9 +/- 19.3 pg/ml) 3 hours after endotoxin was administered, whereas IL-2 levels were decreased (69 +/- 26 U/ml vs 30.6 +/- 14.9 U/ml). IL-4 and IFN-gamma were not detectable in plasma. No changes were seen in the plasma levels of IL-12. Systemic responses did not correlate with changes in cytokine levels. Cytokine patterns found in this study suggest that after low-dose endotoxin administration the T-cell immune response is shifted towards the Th2 cell type response. This early shift towards a Th2 cell response may contribute to the depressed cell-mediated immune response associated with sepsis.
Zimmer
S
S
Shriners Burns Institute, Galveston, USA.
Pollard
V
V
Marshall
G D
GD
Garofalo
R P
RP
Traber
D
D
Prough
D
D
Herndon
D N
DN
D000328:Adult; D001363:Awards and Prizes; D016207:Cytokines / Q000032:analysis* / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism / Q000503:physiopathology; D004731:Endotoxins / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008297:Male; D012016:Reference Values; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000378:metabolism
D016207:Cytokines; D004731:Endotoxins; D007376:Interleukin-2; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma