Increase of anti-inflammatory cytokines in patients with esophageal cancer after perioperative treatment with G-CSF.
Granulocyte colony-stimulating factor (G-CSF) has been shown to effectively stimulate granulopoiesis, in both neutropenic and in non-neutropenic patients. Recently, other effects of G-CSF on the immune system have attracted interest in treating non-neutropenic patients with a high risk of severe infection. In this phase II trial, we measured the effects of G-CSF on the serum cytokine levels in patients with esophageal cancer undergoing esophagectomy. Twenty subsequent patients (study group, 19 evaluable) received G-CSF (rhG-CSF, Filgrastim) at standard doses (300 microg or 480 microg) subcutaneously 2 days before and up to 7 days after surgery. G-CSF was well tolerated. Leukocytes increased from 7600/microl at study entry (day -2) to a maximum of 45 100/microl (day 6). In the study patients, we found a highly significant (P<0.001) postoperative increase of G-CSF, IL-1ra, sTNFRp55 and sTNFRp75 as compared with the baseline level. In contrast, IL-8 levels were decreased by a factor of 6.8; there were no changes in the very low TNF-alpha levels. The comparison of the study group with a control group of 21 cancer patients undergoing major surgery who were not treated with G-CSF showed significant differences in the serum levels of G-CSF, sTNFRp55, sTNFRp75, and IL-1ra, respectively. There was no infection in the study group up to 10 days after surgery as compared with 29.9% in a historical control group (P=0.008). Thus, the induction of anti-inflammatory cytokines and the downregulation of pro-inflammatory cytokines by G-CSF might be a promising adjuvant treatment of infectious complications in patients undergoing esophagectomy.
Hübel
K
K
Department I of Internal Medicine, University of Cologne, Germany.
Mansmann
G
G
Schäfer
H
H
Oberhäuser
F
F
Diehl
V
V
Engert
A
A
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor