Effect of granulocyte colony-stimulating factor on IL-12 p40 production during chemotherapy for B-cell lineage non-Hodgkin's lymphoma patients.
Interleukin (IL)-12 is a 70-kDa cytokine comprised of two disulfide-linked proteins (p35 and p40) and is essential for the initiation of effective immune response. Granulocyte-colony stimulating factor (G-CSF) affects the balance in the production of anti-inflammatory cytokines. We investigated the serum IL-12 p40 and IL-12 Mix (p40 and p70) production in 28 patients with B-cell lineage non-Hodgkin's lymphoma (NHL) treated with chemotherapy (e.g., CHOP regimen) with or without G-CSF administration and eight healthy volunteers. We found that serum levels of IL-12 p40 (191.2 +/- 150.0 pg/mL) and IL-12 Mix (277.4 +/- 274.5 pg/mL) in the patients before chemotherapy were higher than those in the healthy volunteers (IL-12 p40: 76.4 +/- 25.3 pg/mL, IL-12 Mix: 48.5 +/- 33.4 pg/mL) (P = 0.04 and 0.02, respectively). Next, we examined the serum IL-12 p40 and IL-12 Mix levels in nine patients receiving chemotherapy with administration of G-CSF (CG group, n = 9) and without G-CSF (C group, n = 9). Serum IL-12 p40 and IL-12 Mix levels were decreased on 10 d after chemotherapy in both groups, and those in CG groups were significantly lower than those in C group. These results indicated that administration of G-CSF decreased serum IL-12 p40 and IL-12 Mix levels. Overall survival (OS) at 24 months was not significantly different in the two groups (58.3% in group C vs. 80.0% in group CG, P = 0.67). However, the survival rate of patients at clinical stages III and IV in CG group (n = 6, 66.0%) was significantly better than that of patients in C group (n = 4, 25.0%) (P = 0.02). Long-term administration of G-CSF appears to influence the survival rate by reducing immunosuppressive IL-12 p40 production.
Toubai
Tomomi
T
Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. ttoubai@hkg.odn.ne.jp
Tanaka
Junji
J
Ota
Shuichi
S
Fukuhara
Takashi
T
Hashino
Satoshi
S
Kondo
Takeshi
T
Shono
Yusuke
Y
Morioka
Masanobu
M
Kawamura
Tsugumichi
T
Masauzi
Nobuo
N
Kakinoki
Yasutaka
Y
Kobayashi
Hajime
H
Kunieda
Yasuyuki
Y
Kasai
Masaharu
M
Kurosawa
Mitsutoshi
M
Asaka
Masahiro
M
Imamura
Masahiro
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015536:Down-Regulation / Q000187:drug effects*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000097:blood*; D016393:Lymphoma, B-Cell / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011241:Prednisone / Q000008:administration & dosage; D011994:Recombinant Proteins; D015996:Survival Rate; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage
D014408:Biomarkers, Tumor; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone