Effect of granulocyte colony-stimulating factor on IL-12 p40 production during chemotherapy for B-cell lineage non-Hodgkin's lymphoma patients.

Abstract

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.

• Authors: Tomomi Toubai, Junji Tanaka, Shuichi Ota, Takashi Fukuhara, Satoshi Hashino, Takeshi Kondo, Yusuke Shono, Masanobu Morioka, Tsugumichi Kawamura, Nobuo Masauzi, Yasutaka Kakinoki, Hajime Kobayashi, Yasuyuki Kunieda, Masaharu Kasai, Mitsutoshi Kurosawa, Masahiro Asaka, Masahiro Imamura
• Journal: European journal of haematology (Eur J Haematol) Vol. 77 Issue 5 Pg. 403-9 (Nov 2006) ISSN: 0902-4441 [Print] England
• PMID: 16930137 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study)

Chemical References

• Biomarkers, Tumor
• IL12B protein, human
• Interleukin-12 Subunit p40
• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Biomarkers, Tumor (blood)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Down-Regulation (drug effects)
• Doxorubicin (administration & dosage)
• Female
• Gene Expression Regulation, Leukemic (drug effects)
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Humans
• Interleukin-12 Subunit p40 (blood)
• Lymphoma, B-Cell (blood, drug therapy, mortality)
• Male
• Middle Aged
• Neoplasm Staging
• Predictive Value of Tests
• Prednisone (administration & dosage)
• Recombinant Proteins
• Survival Rate
• Time Factors
• Vincristine (administration & dosage)