The relationship of serum IL-6 levels to acute graft-versus-host disease and hepatorenal disease after human bone marrow transplantation.
The potential involvement of cytokines in acute graft-versus-host disease led us to analyze interleukin-6 in serial serum sets from 22 allogeneic marrow recipients who developed either grade 3 or 4 GVHD (n = 10), grade 2 GVHD (n = 6), or grade 1 or no diagnosed GVHD (n = 6). A total of 279 serial serum samples taken three times weekly before day 35 were analyzed. Maximum IL-6 levels were greater than 40 U/ml (range, 40-1536 U/ml), 11-40 U/ml, and less than or equal to 10 U/ml for six, eleven, and five patients, respectively. Serum IL-6 peaks were temporally related to onset of GVHD, onset of a syndrome of hepatorenal dysfunction (HRD), or bilateral lung infiltration. Eight of ten patients who developed grade 3 or 4 GVHD overall had IL-6 maxima of greater than 10 U/ml an average of 1.5 +/- 1.8 days before the clinical onset. Fifteen of 17 patients with peak IL-6 levels greater than 10 U/ml developed symptoms of hepatic and renal dysfunction within three days of the peak, while none of five patients with less than or equal to 10 U/ml of Il-6 developed HRD. Regression analysis demonstrated a linkage between the log magnitudes of the serum IL-6 peaks and onset of either GVHD or HRD within three days (P = 0.001). Furthermore, IL-6 peaks tended to precede GVHD onset for the 10 patients whose GVHD onset and IL-6 peak were within three days of each other (P = 0.02). These results, confirmed by both specific bioassay and by IL-6 ELISA, support the idea that acute GVHD in humans involves a cytokine cascade that includes production of IL-6 in addition to the previously reported involvement of tumor necrosis factor alpha and interferon-gamma.
Symington
F W
FW
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
Symington
B E
BE
Liu
P Y
PY
Viguet
H
H
Santhanam
U
U
Sehgal
P B
PB
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000209:etiology; D006410:Hematopoiesis / Q000187:drug effects; D006530:Hepatorenal Syndrome / Q000097:blood* / Q000209:etiology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged
D015850:Interleukin-6