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

T Toubai, J Tanaka, S Ota, T Fukuhara… - European journal of …, 2006 - Wiley Online Library
T Toubai, J Tanaka, S Ota, T Fukuhara, S Hashino, T Kondo, Y Shono, M Morioka…
European journal of haematology, 2006Wiley Online Library
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
(eg, CHOP regimen) with or without G‐CSF administration and eight healthy volunteers. We …
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.
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